전화번호031-920-1220전 자 우 편[email protected] 색인단어 국문 유방암환자, 삼중음성, 분자표지자, 에스트로겐 수용체, 프로게스테론 수용 체,

기관고유연구사업 최종보고서편집순서 1 : 겉표지 (앞면)

(과제번호 : 0910310-3 )

유방암의 발생 및 치료반응과 관련된 분자적 표지자

개발 및 역학적 특성연구Identification of genetic and epidemiologic factors related to cancer

development and drug-response in breast cancer patients

과제책임자 : 강 한 성

국 립 암 센 터

편집순서 1 : 겉표지 (측면, 뒷면)

(뒷면) (측면)

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5cm

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과

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국

립

암

센

터

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3cm

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1. 이 보고서는 국립암센터 기관고유연구

사업 최종보고서입니다.

2. 이 보고서 내용을 인용할 때에는 반드시

국립암센터 연구사업 결과임을 밝혀야

합니다.

(14 pont, 고딕체)

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6cm↓

편집순서 2 : 제출문

제 출 문

국립암센터 원장 귀하

이 보고서를 기관고유연구사업 “유방암의 발생 및 치료반응과 관련된 분자적 표지자 개발 및 역학적 특성연구” 과제의 최종보고서로 제출합니다.

2011. 12 . 31

국 립 암 센 터

과 제 책 임 자 : 강 한 성연 구 원 : 김 미 경 연 구 원 : 홍 경 만

연 구 원 : 이 근 석 연 구 원 : 이 시 연 연 구 원 : 정 소 연

편집순서 3 : 목차

목 차

< 요 약 문 > (한글)⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯1 (영문)⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯4

1. 연구의 최종목표⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯6 2. 연구의 내용 및 결과⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯8 3. 연구결과 고찰 및 결론⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯27 4. 연구성과 및 목표달성도⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯105 5. 연구결과의 활용계획⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯111 6. 참고문헌⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯112 7. 첨부서류⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯115

- 1 -

< 요 약 문 >연구분야(코드) B-3 과제번호

과 제 명 유방암의 발생 및 치료반응과 관련된 분자적 표지자 개발 및 역학적 특성연구

연구기간/연구비(천원)합계 2009년 1월 ～ 2011년 12월 300,000

1차년도 2009년 1월 ～ 2009년 12월 100,0002차년도 2010년 1월 ～ 2010년 12월 100,0003차년도 2011년 1월 ～ 2011년 12월 100,000

과제책임자 성 명 강 한 성 소 속 유방 내분비암 연구과전화번호 031-920-1220 전 자 우 편 [email protected]

색인단어 국문 유방암환자, 삼중음성, 분자표지자, 에스트로겐 수용체, 프로게스테론 수용체,

영문 breast cancer patients, triple negative, estrogen receptor, progesteron receptor, HER2

◆ 연구목표<최종목표>1. 삼중음성 환자군에서 재발군과 재발하지 않는 군 사이에 암조직에서 발현이 달라지는 유전자에 대한 정보를 기반으로 유방암 환자군에서의 치료 반응 표지자를 개발

2. 삼중음성 환자와 HER2 (+) 환자군, ER (+) 유방암환자군의 유방암 발생 및 재발, 치료반응과 관련이 있는 유전적 변이를 찾고 표지자로 개발

<세부목표>1. 삼중음성 유방암 환자중 재발환자와 그렇지 않은 환자 각각 40명을 선발하고 암조직에서 두 군 사이에 발현이 달라져 있는 유전자 분석

- SPOCK2 유전자의 세포증식 및 in vitro Invasion 억제 효과의 작용기전 연구- SPOCK2 유전자 이외에 선별된 5개 유전자에 대한 특성 연구2. 삼중음성 유방암환자와 정상대조군을 대상으로 암 발생 및 재발(치료반응)과 관련된 380여개 SNP를 분석하여 관련 유전자 규명

◆ 연구내용 및 방법- 삼중음성유방암조직에서 RNA를 분리하고, Illumina expression microarray를 사용하여 발현

을 측정하였다. 이들 중 발현이 재발군과 재발하지 않는 군 사이에 유의한 차이가 있는 유전

자 들을 선발하였으며, 그 차이를 realtime PCR로 다시 확인하였다. 6가지 유전자에 대해 세

포증식과 invasion에 영향을 주는지 여부를 실험하였고 그 중 SPOCK2와 GABRP 두 유전자

에 대한 기능연구를 수행하였다.

-GABRP는 microarray의 결과와 realtime PCR결과를 사용한 모든 결과에서 재발여부와 유의

한 차이가 있었으며, log-rank test로 분석한 결과에서도 유의한 차이를 보였다. GABRP에 대

한 기능적인 연구에서 GABRP의 발현이 암세포의 성장에는 영향이 없었으나, 발현이 증가하

면, invasion과 migration이 줄어든다는 것을 발견하였고, 이러한 현상이 GABRP의 발현이 증

가한 유방암에서 무병생존율이 좋다는 결과와 일맥상통한다고 판단하였다.

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GABRP는 GABA receptor의 한 구성단백질로 알려져 있어서 GABA가 invasion에 미치는 영

향을 조사하였는데, 큰 영향이 없어서 GABRP의 발현은 GABA signal과 무관하게 invasion과

migration에 영향을 주는 것으로 판단하였다. GABRP의 하위신호에서 calcium의 농도가 변하

므로 GABRP의 발현이 실제 calcium level에 영향을 주는 지를 연구하였는데, 역시 GABRP

가 발현되면 세포내 calcium level이 낮아진다는 것을 확인하였다. 또한 GABRP는 EMT

molecule중 E-cadherin을 증가시키고, vimentin을 감소시키는 등 invasion을 감소시키는 변화

와 유의한 관련성을 보인다는 것을 확인할 수 있었다.

- GABRP이외에 SPOCK2에 대한 기능적연구에서 유방암세포의 성장을 촉진하였으며,

invasion을 감소시키는 효과가 있었다. invasion의 감소는 SPOCK2와 Vimentin의 단백질결합

에 의한 감소인 것으로 추정할 수 있었다.

1. 삼중음성 환자와 HER2 (+) 환자군, ER (+) 유방암환자군의 유방암 발생 및 재발, 치료반응과 관련이 있는 SNP 분석

- Aromatase inhibitor 치료 반응과 관련된 유전적 특성과 역학적 특성 연구 (Aromatase inhibitor 치료 환자의 재발군과 비재발군에서 역학적 특성 분석)- ER/PR 양성과 HER2 양성 유방암의 SNP 양상 분석

¡ 384 SNPs 중에서 353개의 SNPs가 실험분석이 완료되었고, 이를 이용하여 유방암 발생과의 관련성을 분석함 . 또한 유방암환자들의 호르몬 양성 여부에 따라 subgroup 분석을 시행함.

¡ Gene-based analysis에서 global p value를 구한 결과, IGF1R가 가장 유의한 유전자로 분석됨(p=0.0003). 이 외에도 MAP2K2, ECHDC1, MAP2K1 등이 유의함

¡ 특히 IGF1, IRS2, IGF1R 유전자는 삼중음성 유방암환자의 발생과 의미있는 관련성을 보임 (p trend = <0.05). IRS2 (4 SNPs)와 IGF1R (23 SNPs)는 BMI와의 상호작용이 있는 것으로 나타남 (P for interaction= <0.05). 이 결과를 통해 이들 유전적 다형성이 비만과의 상호작용을 통해 삼중음성 유방암의 발생에 기여할 것으로 생각됨.

¡ 51 개의 IGF1R SNPs 중에서 3개의 intron에 위치하는 SNPs (rs8032477, rs11635251, and rs12916884)가 유방암의 발생과 유의한 관련성을 보임 (OR(CI 95%) for homozygous genotype (variant genotype): 0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)).

¡ LD 분석을 통해 51 개 IGF1R SNPs를 이용해 분석해보면 7개의 haplotype block이 나왔고 (Figure 5-1~5-4), 그 중에서 하나의 haplotype block (rs4966007, rs8028620, rs4966009, rs8027457, rs4966012, rs1574213, rs11630479)이 유방암 발생과 유의한 관련성이 나타남

논문명 저자(저자구분1)) 저널명(I.F.) Year;Vol(No):Page 구분2)

Genome-wide association study in East Asians identifies novel susceptibility loci for breast 김미경(공동), 강한성(공동) PLoS Genetics(9.543) In press 국외SCI

◆ 연구성과1. 국내 및 국제 전문학술지 논문 게재 및 신청

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cancerGenetic variation in candidate obesity genes IGF1, IRS2, and IGF1R and the risk of triple-negative breast cancer in Korean women

강한성(제1) 김미경(교신) Breast Cancer Research (5.79)2012 (to be communicated)

국외SCIAssociation of polymorphisms and haplotypes in the insulin-like growth factor 1 receptor (IGF1R) gene with breast cancer in Korean women

강한성(제1) 김미경(교신)Breast Cancer Research and Treatment (4.85)

2012 (to be communicated)국외SCI

Methylation patterns of genes coding fordrug-metabolizing enzymes intamoxifen-resistant breast cancer tissues.

강한성(교신)

Journal of

Molecular

Medicine

(5.064)

2010

;88(11):1123-31.국외SCI

Hypomethylation of the interleukin-10 gene inbreast cancer tissues.

강한성(교신)

Breast

(2.172)2010 Jun 18.

국외SCI

Differential methylation hybridization profilingidentifies involvement of STAT1-mediatedpathways in breast cancer.

강한성(교신) Int J Oncol. 2011 Oct;

39(4):955-63.국외SCI

Accumulation of p53 determined byimmunohistochemistry as a prognostic marker innode negative breast cancer; analysis accordingto St Gallen consensus and intrinsic subtypes.

강한성(교신)

J SurgOncol.

2011 Mar1;103(3):207-11.

국외SCI

Predictor of recurrence in the triple negativebreast cancer (tentative)

논문명 저자 학술대회명 지역1)

Association of polymorphisms and haplotypes in the

insulin-like growth factor 1 receptor (IGF1R) gene with

breast cancer in Korean women.

김 미 경 , 강 한

성, 홍경만

미국암학회(AACR) 미국, 시

카고

2. 국내 및 국제 학술대회 논문 발표

<정성적 성과>

1) 삼중음성과 HER2양성 유방암의 군을 치료반응에 따라 유전적으로 분류하고 이들의 특성을 연구하며 이를 바탕으로 진료 및 치료 지침을 개발할 수 있음 2) 유방암의 각 군마다 특징적인 예후인자 규명을 통해 3차 예방을 위한 전략 수립이 가능 3) 한국 유방암 환자에서 환자군에 따른 맞춤형 치료의 기본 단서가 되며 환자의 예후를 판단할 새로운 치료 예측 진단 키트 개발

◆ 참여연구원(최종연도 참여인원) 성 명

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Title of Project Identification of Genetic and Epidemiologic Factors Related to Cancer Development and Drug-Response in Breast Cancer

Key Words BMI, IGF1, IGF1R, IRS2, Obesity, Single Nucleotide Polymorphism (SNP), Triple-negative breast cancer

Project Leader Associated CompanyIn our effort to find new markers in subgroups of breast cancer, we identified two candidate

genes, SPOCK2 and GABRP, of which functions are related to proliferation or invasion in

breast cancer. Especially, higher expression of GABRP was significantly associated with

non-recurrent cases and with better disease-free survival for triple negative breast cancer

(TNBC). In the functional studies, SPOCK2 induced proliferation, but reduced the invasion of

breast cancer cells. The reduced invasion by SPOCK2 might be related to the interaction

between SPOCK2 and VIMENTIN. GABRP showed no effect on cell growth, but reduced

invaion and migration of breast cancer cells. The effect on invasion was independent with

GABA receptor, and GABRP reduced intracellular calcium level. In addition, GABRP expression

reduced the level of VIMENTIN but increased the level of E-cadherin, which are consistent

with the reduced invasive activity of cells expressing GABRP.

Association of polymorphisms and haplotypes in the insulin-like growth factor 1 receptor (IGF1R) gene with breast cancer in Korean womenAbstract: The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase growth factor receptor that plays important roles in numerous cellular functions and signal transduction pathways. IGF1R may also play a role in the initiation and progression of breast cancer. However, studies of common variation in the IGF1R gene, involved in steroid hormone and IGF-1 metabolism, have yet to provide convincing evidence that such variants predict breast cancer risk. We genotyped 384 tagging single nucleotide polymorphisms (SNPs) in 1026 cases of breast cancer and 392 age-matched control in a population of Korean women. Of the 384 SNPs, fifty one SNPs in the IGF1R gene were examined for association with breast cancer in the study. All the SNPs investigated were in Hardy-Weinberg equilibrium. These SNPs tested were significantly associated with breast cancer risk, after correction for multiple comparisons stratified by adjusting for age at diagnosis, BMI, age at menarche, and age at first parturition. Among 51 IGF1R SNPs, three intron located SNPs (rs8032477, rs11635251, and rs12916884) with homozygous genotype (variant genotype) had increased risk of breast cancer (OR(CI 95%): 0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)). Seven of the 51 IGF1R SNPs were in LD and in one haplotype block, and were likely to be associated with breast cancer risk. Overall, this comprehensive case-control study found statistically significant associations between breast cancer risk and polymorphisms in IGF1R gene.

Project Summary

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Genetic variation in candidate obesity genes IGF1, IRS2, and IGF1R and the risk of triple-negative breast cancer in Korean womenAbstract: Obesity has consistently been associated with breast cancer risk. An insulin-related pathway to breast cancer has been hypothesized. The interaction of these genes and BMI in triple-negative breast cancer (TNBC) has not been previously studies. We conducted a case-control study among Korean women to determine whether genes associate with obesity and TNBC risk. SNPs were selected for common variation across three genes: IGF1, IRS2, and IGF1R. Eight out of 23 SNPs in IGF1, eight out of 11 SNPs in IRS2, and twenty nine out of 51 SNPs in IGF1R were associated with TNBC risk (p trend = <0.05). Among these, four SNPs in IRS2 and twenty three out SNPs in IGF1R were associated with TNBC risk and high BMI (P for interaction= <0.05). Our findings suggest that these SNPs may harbor the risk for TNBC, and these associations may be influenced by obesity or high BMI.

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구분 목표 내용 및 범위

1차년도(2009)

삼중음성(triple negative) 유방암환자의 항암제 치료 반응과 관련된 유전적 특성 규명과 역학적 특성 연구

1.유전적 특성 규명2.치료반응 관련 분자적 표지자 개발 및 치료반응에 미치는 영향 규명3.치료반응에 미치는 역학적 요인 및 예후인자 규명

유방암환자의 발생에 미치는 요인에 대한 역학연구

삼중음성(triple negative) 유방암환자의 발생 위험요인 규명

2차년도(2010)

유방암의 재발과 관련된 유전적 특성 규명과 역학적 특성 연구



삼중음성(triple negative) 유방암환자의 발생에 미치는 요인에 대한 역학연구

3차년도(2011)

Aromatase inhibitor 치료 반응과 관련된 유전적 특성 규명과 역학적 특성 연구



삼중음성(triple negative) 유방암환자의 발생에 미치는 요인에 대한 역학연구

1. 연구의 최종목표

1. 삼중음성와 HER2 (+) 환자군에서 재발군과 재발하지 않는 군 사이에 암조직에서 발현이 달라지는 유전자에 대한 정보를 기반으로 두가지 유방암 환자군에서의 치료 반응 표지자를 개발

2. 삼중음성 환자와 HER2 (+) 환자군, ER (+) 유방암환자군의 유방암발생과 관련이 있는 유전적 변이를 찾고 표지자로 개발

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￭ 유방암환자 Follow-up 연구

1. 삼중음성 유방암환자와 ER (+) 및 HER2 (+) 환자군에서의 치료제 반응 표지자 개발 및 역학적 연구. 구체적으로 삼중음성 유방암환자와 ER(+) 유방암환자에서 치료반응군과 반응하지 않는군을 각각 40명씩 선발하고 expression array를 시행하고, HER2 (+)군에서는 치료반응군과 그렇지 않는군을 각각 30명씩 선발하여 expression array를 시행함으로써 치료반응과 관련된 분자적 표지자를 개발

2. 삼중음성 유방암 환자에게서 호르몬 수용체나 호르몬 대사 관련 유전자의 단일염기변이를 분석하여 개별 유전자의 유전적 다형성과 유방암의 치료반응 및 생존율에 대한 영향을 규명하고, 각기 다른 유전형에 따른 임상적 특성 및 환경적 인자와의 상호관련성이 유방암치료반응 및 생존율에 미치는 영향을 규명하고자 함. 유전적 다형성이 수술 후 생존율(overall survival, disease-free survival)에 영향을 평가하고, 특히 치료방법에 대한 반응도에 차이가 있는지를 평가함으로서 이들 요인의 독립적 예후인자로서의 의미를 규명하고자 함.

￭ 유방암 case-control 연구

1. 삼중음성 유방암 환자의 발병위험 요인에 대한 역학적 특성과 호르몬 수용체나 호르몬 대사 관련 유전자 (ESR1, ESR2, CYP1A1, CYP1B1, COMT)의 단일염기변이(single nucleotide polymorphism)를 분석하여 개별 유전자의 유전적 다형성 및 haplotype과 유방암의 발생에 대한 영향을 규명하고, 각기 다른 유전형에 따른 임상적 특성 및 환경적 인자와의 상호관련성이 유방암 발생에 미치는 영향을 규명하고자 함.

2. 유방암의 중요한 위험요인인 생식력, 호르몬, 비만 등에 따른 이들 요인 및 유전적 다형성과의 관련성의 차이를 평가

3. 유방암의 아형별로 위험요인 및 유전적 다형성과의 관련성의 차이를 평가하여 각 위험요인의 관련성이 각각 다른지를 조사하고, 이에 영향을 주는 위험요인과의 관련성을 평가4. 유방암환자와 대조군의 약 1500여명의 혈액 DNA에서 400여가지 SNP를 분석하고 임상적 혹은 영양학적인 profile과 유방암의 subtype별 연관성을 연구하는 실험 중, 1차년도에 삼중음성 유방암 환자를 대상으로 약 250여명의 환자와 100여명의 대조군에 대한 SNP를 분석할 예정임.

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2. 연구 내용 I. 삼중음성 환자중 재발군과 재발하지 않는 군 사이의 암조직에서 발현이 달라지는 유전자의 연

구

1) 삼중음성 유방암조직의 H&E 염색 및 cryo-microtome을 이용한 section.

Remove

pre post

그림1. 유방암조직 중 염증세포가 많은 부분과 암세포가 적은 부분을 잘라내고 난 이후 다시 H&E염색

을 시행하여 남은 부분의 암조직에 암세포가 적어도 50% 이상 존재한다는 것을 확인한 다음 조직을

cryosection하여 eppendorf tube에 모은 후 RNA를 분리하였음. cryosection이후 다시 암조직에서 암세

포가 차지하는 부분을 확인하여 거의 비슷한 경우에만 cryosection으로 모은 조직을 실험에 사용하였

음.

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그림 2. 유방암 조직과 정상조직의 H&E염색 사진의 예. cryosection이전과 이

후의 조직을 H&E염색을 시행하여 모두 조직에서 유방암세포가 50%이상 차지

하고 있다는 것을 확인함.

그림 1, 그림2와 같이 모든 유방암 혹은 정상 조직에 대해 cryosection이전과 이후의 H&E 염색을시행

하고 결과를 electronic file로 보관하였음.

2) cryosection한 유방암 혹은 정상조직에서 RNA의 분리 및 전기영동을 통한 RNA quality check.

cryosection한 유방암 혹은 유방 정상조직에서 RNA를 분리하여 그 quality를 전기영동을 시행하여 그

림 3과 같이 확인하였다. 대부분의 조직에서 얻은 RNA는 quality가 양호하였으나 일부 조직에서 분리

된 RNA양이 적어서 quality를 확인하기 어려운 경우 혹은 quality가 나쁜 경우는 실험을 진행하지 않

았음.

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그림 3. RNA를 분리한 후 전기영동으로 RNA quality를 점검한 결과

3) Illumina expression microarray를 사용하여 50개 유방암 혹은 정상 유방조직에서의 발현양 비교결

과.

1년차에 60개의 삼중음성유방암조직에 대한 발현을 보고하였으나 나중에 이들의 삼중음성여부를 다시

review한 결과 최종적으로 50개만 삼중음성유방암조직이라는 것을 확인하고, 이들 50개의 유방암조직에

대해서만 분석을 시행하였음. Illumina expression microarray는 성공적으로 이루어졌고, 이들 중 recur

한 유방암과 recur하지 않은 유방암 사이의 유의한 발현 차이를 t-test로 검증하였고 t-test상 유의한

경우에 각각의 유전자 발현 양상을 그래프로 그려서 최종적으로 recur한 유방암에서 유의하게 증가하

거나 감소한 유전자들을 선발하였다. SPOCK2의 경우 최종 50개 삼중음성 유방암조직 중 재발한 군과

재발하지 않은 군에서 t-test에서 유의하지 않았지만 2차년도 실험에서는 유의한 것으로 생각하고

functional study를 진행하여 proliferation과 invasion에 영향을 준다는 것을 알게되어서 이에 대한 실험

을 계속 진행하였다.

4) Real Time PCR

각 시료의 RNA로 부터 cDNA를 합성하고, 선별된 27개 유전자에 대한 Real Time PCR을 각각 실시

하였다. 분석된 결과 중, expression array결과와 동일하거나 유사한 양상을 보이는 유전자를 최종적으

로 선발하였는데, SPOCK2 를 포함한 6종 유전자가 최종적으로 선발되었다.

5) 선별된 유전자의 클로닝 및 삼중음성 유방암 세포주에 transfection 도입

Real Time PCR 결과와 Expression assay 결과가 유사한 양상을 보이는 유전자를 최종적으로 6개 선

별하였고, 이들 유전자중 우선, SPOCK2와 GABRP 유전자에 대한 기능적연구를 우선 진행하기로 하였

음.

이들 유전자는 PCR을 이용 증폭하여, eukaryotic 발현 벡터인 pcDNA3.1 로 클로닝하였다. 클로닝된

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유전자는 삼중음성 유방암 세포주인 MB231, HS-578T 와, MCF7 등 여러가지 유방암 세포주에 도입하

였다. 유방암 세포주는 대개 transfection 효율이 낮아서, transient 상태의 분석으로는 도입된 유전자의

효과를 분석하기 어려우므로, stable cell-line 을 만들어 사용하였다. Transfection 시킨 세포주는 선별

마커인 G418 항생제를 이용, 2주간 선별과정을 거쳐, SPOCK2 가 상시적으로 발현되는 stable cell-line

클론 콜로니들을 얻었고, 각 클론들의 변이를 최소화 하기위해, 클론들을 모두 pooling 하여 사용하였

다.

그림4. SPOCK2 유전자의 Expression array와 Real Time PCR 결과값의 비교

6) SPOCK2유전자의 세포증식에 대한 효과: SPOCK2 유전자가 도입된 유방암 세포주와, 이와 비교

하기위해 pCDNA3.1 vector만 도입시킨 세포주를 대상으로 세포증식 분석을 실시하였다.

pCDNA3.1 vector만 도입시킨 세포주에 비해서 SPOCK2 유전자를 도입시킨 유방암 세포주의 세

포증식이 더 빠른 것을 발견하였다 (그림 5). 이는 일부 유방암세포에서 SPOCK2가 과발현되어

있다는 것을 발견하였는데, 이러한 암에서 SPOCK2가 암세포의 증식에 관여할 것이라는 것을 의

미한다.

7) SPOCK2유전자의 세포침윤에 대한 효과: : SPOCK2 유전자가 도입된 유방암 세포주의 stable

cell-line을 대상으로 Matri-gel invasion assay 를 실시하였다. Matri-gel 이 코팅된 membrane을

통과한 세포수를 측정함으로써, 세포주의 Invasion 활성을 in vitro 상으로 측정하였는데, SPOCK2

유전자가 도입된 유방암 세포주의 invasion 활성이 감소하는것을 확인하였다 (그림6). 이는

SPOCK2의 발현이 암세포의 증식을 촉진시키지만, 암세포의 침윤은 감소시킬수 있다는 것을 의미

한다.

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그림5. Spock2 유전자가 도입된 유방암세포주의 세포증식 분석실험

(Mock; pcDNA3.1, Spock2; pcDNA3.1-Spock2)

그림6. SPOCK2가 도입된 유방암 세포주, MCF7과 MB231에서의 in vitro Invasion assay

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8) SPOCK2 immunoprecipitation을 통한 결합단백질의 스크리닝 및 IP 단백질의 MASS 분석

SPOCK2 단백질과 결합하는 세포내 단백질을 분석하기 SPOCK2 단백질을 cooupling시킨 resin에

cytosolic protein을 결합시키고, washing한 후 결합한 단백질들을 SDS-PAGE로 분석하고,

MALDI-TOF MASS 분석을 실시하였다. 분석결과 Vimentin 단백질이 특이하게 검출되었는데,

이는 Vimentin이 SPOCK2 단백질과 상호작용하는 것으로 해석할 수 있다 (그림7).

그림7. 재조합 SPOCK2를 결합시킨 resin에 cytosolic protein을 결합시킨 후 침전된 단백

질들을 MALDI-TOF MASS로 분석한 결과. 두가지 단백질이 분석되었는데, SPOCK2 (or

testican-2) 와 또 다른 단백질인 Vimentin이 발견되었음.

9) GABRP는 최종 50예의 삼중음성 유방암에서도 재발한군과 재발하지 않은 군에서 유의한 차이

를 보였으며, expression array를 사용한 경우와 RT-PCR을 이용한 방법 모두에서 유의한 차이를

보여 (그림 8) GABRP의 발현이 삼중음성유방암의 생존과 관련이 있을 것으로 생각하였다.

GABRP와 무병생존율과의 상관관계를 확인하기 위하여 Kaplan-Meier plot하였고, log-rank test

에서 expression array결과와 RT-PCR결과 모두에서 유의하게 차이가 있다는 것을 확인하였다

(그림 9). log-rank test를 위하여 GABRP의 발현정도가 높은 군과 낮은 군으로 나누고, 이 두 군

의 수를 모두 25명 씩 같이 만들어 분석하였다. 이러한 결과는 GABRP가 발현이 높은 경우 유의

하게 생존이 좋아진다는 것을 의미한다. 이렇게 GABRP 발현과 생존과의 관련성이 어떠한

biological background에서 나오는 지를 알아보기 위하여, GABRP의 발현이 암세포의 성장과

invasion혹은 migration에 어떠한 영향을 미치는 지를 알아보기 위하여 실험을 진행하였다.

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그림 8. 삼중음성 유방암 중 재발군과 재발하지 않는 군에서 GABRP의 발현양상

그림 9. GABRP의 발현이 높은 군과 낮은 군으로 나누어 Kaplan-Meier plot을 하고, log-rank

test로 유의성을 확인한 그림. Q-PCR을 사용하거나 expression array결과를 사용한 모든 결과에

서 두 군간의 발현에 차이가 유의하다는 것을 확인할 수 있었다.

10) GABRP를 발현하지 않는 MCF7과 MDA-MB-231세포에 GABRP를 과발현하여도 growth에

는 영향이 없다는 것을 확인하였다 (data not shown). 따라서 GABRP가 세포의 성장에는 영향을

주지 않는 것으로 판단하고, invasion과 migration assay를 시행하였는데, GABRP가 MCF7과

MDA-MB-231세포의 invasion과 migration을 억제한다는 것을 확인하였다 (그림 10, 그림 11, 그

림 12).

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그림 10. GABRP를 발현이 MB-231세포 migration에 미치는 영향. GABRP를 발현하지 않는

MDA-MB-231세포에 발현시킨 후 migration을 비교하였는데, 발현하는 세포에서 migration이 줄

어든다는 것을 확인하였다. GABRP를 발현하는 세포는 G418로 selection하여 선택한 후 실험에

이용하였다. MCF7 세포에서도 같은 결과를 얻었다.

그림 11. GABRP발현이 invasion에 미치는 영향. GABRP를 발현하지 않는 MDA-MB-231세포와

MCF7세포에 GABRP를 발현시켜서 invasion에 미치는 영향을 비교하였는데, 두 세포 모두에서

유의하게 invasion이 감소하는 것을 확인하였다.

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그림 12. GABRP의 발현과 invasion과의 관련성. GABRP발현이 invasion과 관련이 있다는 것을

다시 확인하기 위하여 GABRP발현으로 invasion이 감소한 세포에 GABRP siRNA를 처리하면

scrambled siRNA를 처리한 세포에 비해 현저히 invasion이 증가한다는 것을 확인할 수 있었다.

11) GABRP의 발현이 invasion과 migration을 유의하게 감소시킨다는 것과 GABRP의 발현이 높

은 군에서 DFS(무병생존율)이 좋다는 사실이 서로 일치한다는 것을 알 수 있다. 다음으로는

GABRP의 발현변화가 세포에 어떠한 영향을 미쳐서 invasion이나 migration에 변화를 가져오는

지를 알아보기 위하여, 우선 GABRP가 GABA receptor의 한 구성분자이므로 GABA를 처리하여

GABRP의 과발현과 같은 효과가 있는 지 여부를 확인하기 위하여 MDA-MB-231과 MCF7 세포

에 GABA를 처리하고 invasion에 미치는 영향을 측정하였다. 이들이 invasion에 미치는 영향은 그

림 13에 보는바와 같이 거의 없거나 미미하였다. 유방암세포는 GABA를 통해 신호를 전달하는

nerve와 contact되어 있다는 증거가 아직까지 보고되지 않았기 때문에, 이들에 미치는 GABA의

농도는 혈액에 있는 GABA의 농도정도이거나 오히려 낮을 수 있다고 판단할 수 있다. 실제

GABA가 이들의 암세포에 미치는 영향이 100ug이하일 것이라고 생각한다면, GABA receptor를

통하여 GABRP를 경유하는 신호전달에 의한 invasion의 변화는 거의 없다고 판단할 수 있다. 따

라서 GABRP의 발현에 따른 invasion의 변화는 GABA의 신호와는 무관하다고 판단하였고,

GABRP가 세포의 이동과 invasion에 미치는 영향은 GABRP와 세포내 또 다른 단백질과의 상호

작용일 것으로 판단할 수 있다.

- 17 -

그림 13. GABA가 invasion에 미치는 영향. MDA-MB-231은 GABRP가 발현되지 않은 세포로 이

들을 처리하여 나타나는 변화는 GABRP와 무관하다고 할 수 있다. 그런데 GABA를 처리하여도

invasion에는 아무런 변화가 없었다. GABA의 양을 500uM로 처리하여도 약간의 변화를 보이기는

했지만 그 변화량이 GABRP의 발현에 의한 차이보다 훨씬 미미하다는 것을 확인할 수 있었다.

12) GABRP는 GABA receptor의 신호를 받아 세포내 calcium level을 변화시킨다는 것이 알려져

있다. GABA의 신호 없이도 GABRP가 세포내 calcium level을 변화시키는 지 여부를 확인하기

위하여 GABRP가 발현된 세포에서 세포내 calcium level의 변화를 측정하였는데, GABRP가 세포

내 calcium level을 낮춘다는 것을 확인하였다 (그림 14).

13) GABRP의 과발현이 EMT pathway와 관련된 분자들에 미치는 영향을 보기위해 RT-PCR로

발현의 변화를 관찰하였는데, GABRP를 발현한 세포에서 E-cadherin의 발현은 증가하고,

Vimentin의 발현은 줄어든다는 것을 확인하였는데 (그림 15), 이는 GABRP의 발현이 EMT

pathway에도 영향을 준다는 것을 확인할 수 있다.

- 18 -

그림 14. GABRP를 발현과 세포내 calcium level과의 상관관계. GABRP를 발현하는 세포가 발현

하지 않은 세포에 비해 세포내 calcium level이 유의하게 낮다는 것을 확인할 수 있다.

그림 15. GABRP의 발현이 E-cadherin과 Vimentin의 발현에 미치는 영향. GABRP를 발현하지

않는 MCF7 혹은 MDA-MB-231세포에 GABRP를 발현시키면, E-cadherin의 발현은 증가하고,

Vimentin의 발현은 감소하였다. 이러한 결과는 GABRP의 발현이 invasion혹은 migration을 감소

시킨다는 결과와 일맥상통한다고 할 수 있다.

- 19 -

FIGURE 1. 연구 내용 본 연구 체계의 장점은

l 먼저 국립암센터 종양 은행에 보관 중인 종양 조직과 환자의 혈액은 보관 상태가 매우 양호하여 DNA, RNA그리고 단백질과 관련된 다양한 연구도 가능함. 또한 환자의 임상 자료도 체계적으로 정리돼 있고 이들의 임상 경과도 데이터 베이스화 하였기 때문에 특정 표지자를 발견하면 바로 생존율을 비교하여 validation이 가능함.

l 인적 구성 측면에서 본 연구에서는 분자생물학자(홍경만), 분자역학자(김미경), 그리고 임상의사(강한성, 노정실, 이근석, 이시연, 정소연) 등이 포함되어 다양한 학문적 접근 방식을 통하여 한국형 유방암의 약제 내성과 관련된 유방암의 약제 내성 유발인자를 규명하고자 함. 이런 인적 구성은 기존의 한가지 방법으로 진행하는 연구의 한계점을 개선하여 다양한 의견 개진과 회의를 통해 통합적 모델제시

l 이런 연구 방식은 특정 내성 유발 물질이 밝혀지면 임상적, 분자 생물학적으로 바로 확인이 가능하여 환자의 맞춤형 치료의 기초 단서가 됨.

- 20 -

본 과제는 크기 유방암의 subgroup별 치료반응과 관련된 유방암표지자 개발에 관한 내용과 유방암 subgroup별 암발생과 관련된 SNP발굴에 대한 두가지 내용으로 구성되고 있으며, 연차마다 유방암의 subgroup별 연구를 진행함. 이 각각의 추진전략 및 방법에 대해 구체적으로 기술하면 다음과 같음.

FIGURE 2. 연구수행체계

- 21 -

20-29 30-39 40-49 50-59 60-69 70-79 80- Total

Breast cancer

luminal A 10 148 400 175 0 34 4 771luminal B 1 41 93 45 0 4 0 184HER2-overexpression 0 22 51 60 0 8 1 142Triple-negative 5 48 94 46 0 5 1 199

Female HR+ 13 187 472 185 112 31 3 1003(HER2:2+) HR- 2 27 38 34 27 1 1 130Total 31 473 1148 545 139 83 10 2429

1) 유방암 subgroup별로 암발생과 관련있는 SNP 발굴: HER2, ER, PR 여부에

따른 비교

(1) 연구대상자

2003년부터 2007년까지 유방암으로 진단받고 수술/치료를 받은 환자 중(2,429명) 조직학적으로 확진되고 IHC가 판독 가능하면서 DNA가 유용한 여성 유방암 환자와 조직 검사를 통해 암이 발견되지 않은 대조군을 대상으로 함

Table 1. Age distribution of study subjects(Year 2003∼2007)

(2) 기관윤리심사위원회 및 생명윤리 심사위원회 심의 본 연구의 환자 모집 방법, 조사 내용(개인 정보 및 유전자 검사), 가능한 부작용, 연구 참여자의 권익 등 연구 전반에 관한 윤리적 검토를 받음. 고지된 동의서 문구에 대한 심의를 받음

(3) 임상 조사 임상양상 및 임상경과 조사(35세 이하의 연도별 환자 수, 환자 분포 % , 생존율, 병기별 생존율, 임파선전이 %), 병기, 호르몬 수용체(ER과 PR) 양성비율 차이, 조직분화도 등급의 차이, 혈관림프관침윤 차이, 폐경 여부, 치료 방법 등 조사 (4) 위험요인 및 생활습관 조사 인구학적 요인, 생식력, 흡연력, 음주력, 사회경제적 요인, 질병력, 가족력 등, 기타 관련 요인

(5) 혈액 또는 수술/조직검사를 통해 얻은 파라핀 블록으로부터 genomic DNA 추출buffy coat 또는 파라핀 블록에 RNase와 proteinase K 처리 후 단백질을 제거하고 DNA를 추출하여 분석 직전까지 -20〫C에서 보관.

- 22 -

Gene Full name Gene Full nameABCB1 ATP-binding cassette sub-family

B member 1, P-glycoprotein ERBB2 E-erb-b2 AR Androgen receptor ESR1 Estrogen receptor 1 geneATM Ataxia telangiectasia mutated ESR2 Estrogen receptor 2 geneATP1B2 ATPase, Na+/K+ transporting, beta

2 polypeptide FLJ45983 FLJ45983 protein AXIN2 Axin 2 GATA3 GATA binding protein 3 BARD1 BRCA1 associated RING domain 1 GPX1 glutathione peroxidase 1 BRCA1 Breast cancer 1 GPX4 glutathione peroxidase 4

(phospholipid hydroperoxidase) BRCA2 Breast cancer 2, early onset GSTP1 Glutathione S-transferase piCCND1 Cyclin D1 IGF1 Insulin-like growth factor 1

(somatomedin C) CCND3 Cyclin D3 IGF1R Insulin-like growth factor 1

receptor COMT Catechol-O-methyl transferase MDM2 MDM2CYP1A Cytochrome P450, family 1,

subfamily A, polypeptide 1 MTHFR Methylenetetrahydrofolate reductase

CYP1B1 CYP1B1 belongs to the cytochrome P450 super family of enzymes. PGR Progesterone receptor gene

DHFR Dihydrofolate reductase RAD51 RAD51 homolog SOD2 Superoxide dismutase 2,

mitochondrial TYMS Thymidylate synthetase or TS TP53 Tumor protein p53 WDR79 WD repeat domain 79

(6) 유전적 다형성 분석

Table 2. Candidate gene genotyped in this study.

- SNP의 분석을 위해서는 약 380여개의 SNP를 한꺼번에 확인할 수 있도록 custom made SNP array chip을 제작할 예정이며, 이 array chip을 이용하여 환자시료의 SNP를 분석항 예정임. 간단히 방법을 기술하면 확보된 시료로 구성된 96 plate set를 이용하여 streptavidin과 biotin을 넣어 DNA를 활성화시키고 활성화된 DNA에 allele specific oligo, locus specific oligo, universal PCR primer (oligo pool)를 넣어 hybridization함. 각 후보 marker에 특이적으로 binding된 oligo와 primer는 extension, ligation 과정을 거쳐 PCR 반응을 하고 각 시료별, marker 별로 특이적으로 생성된 형광 probe를 Bead bundle에 붙이고 BeadArray reader (Illumina)를 이용하여 각 시료별로 형광이미지 (scanning image)를 구현함. 각 후보 marker의 genotype은 자동으로 calling되며, 이러한 원본 결과를 분석에 이용함. 이과정의 설명은 다음 그림과 같음.

- 23 -

제작된 probe는 하나의 oligo pool을 구성함

Golden Gate Assay 방법의 전체 과정

FIGURE 3. SNP 분석 과정

- 24 -

Figure 4 . Selection of candidate SNP

2) 유방암 환자군에서 재발과 관련된 SNP 연구

(1) 연구대상자

¡ 2003년부터 2007년까지 유방암으로 진단받고 수술/치료를 받은 환자 중 조직학적으로 확진되고 IHC가 판독 가능하면서 DNA가 유용한 여성 유방암 환자 307명 중에서 재발군(26명)과 비재발군(281명)을 대상으로 함

(2) 위험요인 및 생활습관 조사 인구학적 요인, 생식력, 흡연력, 음주력, 사회경제적 요인, 질병력, 가족력 등, 기타 관련 요인

3) Aromatase inhibitor 치료 반응과 관련된 역학적 특성 연구(1) 연구대상자

2001년부터 2008년까지 유방암으로 진단받고 수술/치료를 받은 환자중 조직학적으로 확진된 여성 유방암 환자(2,429명) 중에서 종양은행에 genomic DNA 추출 가능한 혈액이 보관되어 있는 대상자. 이 중에서 2010년 당해연도에는 Aromatase inhibitor 치료환자 418명을 대상으로 함

- 25 -

Cytokine & growth factor17 Gene55 SNP

FGFR2 16

DNA repair/break16 Gene65 SNPs

ATM 3IGF-1 16 ATP1B2 3IGF1 1 BARD1 8IGF1R 2 BRCA2 2IGFBP3 3 CHEK2 1ITGA3 1 ERCC2 1ITGA6 1 HER2 20ITGAv 1 LIG4 1ITGB3 1 NBS1 1ITGB4 1 NBS1 or NBN 1ITGB5 1 RAD51 1MAP3K1 3 TP53 12TGFB1 2

WDR79 4TNRC9 or TOX3 1XRCC1 1TNRC9, LOC643714 1XRCC2 3TNRC9/LOC643714 3XRCC3 3TOX3 1

Drug response11 Gene13 SNPs

ABCB1 3

Hormone metabolism6 Gene75 SNPs

AR 6CYP19 1 ERBB2 1CYP20 1 ESR1 32CYP21 1

ESR2 8DHFR 1PGR 25GSTP1 1

L55M 1 STE or SULT1E1 3MTHFR 1

transcription factor4 Gene6 SNPs

A2BP1 1Q129R 1EHMT1 1TP53 1FLJ45983 1TYMS 1

Early-onset BR6 Gene15 SNPs

COMT 1 GATA3 3CYP1A1 1

tumor suppressor4 Gene17 SNPs)

APC 11CYP1B1 3 LSP1 4ESR1 6 ODC 1ESR2 3 RIZ1 or PRDM2 1MDM 1

(2) 위험요인 및 생활습관 조사 인구학적 요인, 생식력, 흡연력, 음주력, 사회경제적 요인, 질병력, 가족력 등, 기타 관련 요인Table 3-1. The selected 384 SNPs for candidate gene approach

- 26 -

Others24 Gene31 SNPs

16q12 1

Xenobiotics Metabolism24 Gene52 SNPs

ADH1B 22p(19150424) 1 ADH1C 22q35 2 AURKA 15p(45321475bp) 1 AXIN2 55p12 1 BAT8 or EHMT2 15p13 1 CASP8 25p14 1 CCND1 55p15 1 CCND3 15p16 1 CCNE1 15p17 1 CDK6 15p18 1 CDKN1A 25q(52454339bp) 1 CDKN1B 18q(128424800) 1 CDKN2A 18q24 2 DNMT3A 1ECHDC1 4 DNMT3B 1H19 1 GPX1 1MCS5A6 1 GPX4 1MMP8 1 HSD11B1 5MRPS30 1 ICAM5 1PHKA1 1 IRS2 11RB1 2 NUMA1 1RNF146 1 PTGIS 3

SHBG 1STK15 or AURKA or ZNF43

1

SOD2 2 TBXAS1 1

Table 3-2. The selected 384 SNPs for candidate gene approach (continued)

- 27 -

3. 연구결과 및 결론- 삼중음성유방암에서 재발과 유의하게 관련되어 있는 분자적인 변화를 찾는 연구에서 20여 가지

유전자를 찾았는데, 그 중 invasion과 migration에 유의한 변화를 주는 것은 GABRP와

SPOCK2 등 두가지 뿐이었다. 따라서 이들에 대한 기능적인 연구가 삼중음성 유방암 혹은 유

방암의 재발과 관련되어 중요한 실마리를 제공해 줄 수 있을 것으로 판단하여 이들에 대해

좀 더 연구를 진행하였다.

- GABRP에 대한 국내외 연구는 많이 진행되지는 않았다. GABRP의 발현이 유방암에서 유의하

게 증가되어 있다는 보고 (Zafrakas et al., 2006) 가 있는 반면에 발현이 감소되어 있다는 보

고 (Symmans et al., 2005)도 있어서 실제 유방암에서 GABRP의 증감여부는 GABRP가 발현

되는 세포의 종류와 분포에 따라 다를 수 있다는 것을 알 수 있다. 우리의 결과에 의하면 정

상적인 유방조직에 비해 암에서 GABRP가 상대적으로 증가되어 있는 암들이 있다는 결과를

얻었다.

- GABRP가 증가되거나 감소되는 것에 따른 암환자의 생존율과의 상관관계에 대해서는 알려진

바가 없다. 삼중음성유방암에서 GABRP의 발현이 높아져 있는 환자들이 상대적으로 무병생

존율이 높다는 결과는 본 연구에 의해 처음 밝혀지게 되었다. 다만 GABRP의 발현이 삼중음

성유방암에서 상대적으로 발현율이 높다는 것이 보고되었다 (Symmans et al., 2005).

- GABRP의 발현이 무병생존율과 관련이 있다는 것을 본 연구에서 처음 밝히게 되었는데, 그 생

물학적인 원인을 알아내기 위하여 기능적 연구를 수행하였다. 본 연구의 결과에서 GABRP를

발현하는 것이 암세포의 성장에는 영향이 없었는데, migration과 invasion을 감소시킨다는 것

을 발견하였고, 이것이 무병생존율의 상대적인 증가와 관련된 것으로 추정할 수 있다.

GABRP의 발현이 췌장암세포의 성장을 촉진시킨다는 논문이 발표된 바가 있으며 (Takehara

et al., 2007), GABRP의 발현과 migration혹은 invasion과의 관련성은 현재까지 보고된 바가

없다.

- GABRP의 발현과 migration혹은 invasion과의 관련성이 GABA에 의한 신호전달과 관련이 있는

지 여부를 확인하는 실험을 진행하였다. 이미 GABA가 invasion 혹은 proliferation과 관련되

어 있다는 보고가 있었다 (Joseph et al., 2002). 그런데 GABRP는 GABA receptor 중 한 구

성단백질로 알려져 있으며, GABA가 GABA receptor에 결합하여 발생하는 신호를 GABRP가

세포내로 전달한다고 알려져 있다. 그러나 현재까지 GABA관련된 신경세포가 유방암세포 각

각에 분포한다는 증거는 보고된 바가 없으며, 암세포에서 GABA receptor의 구성 단백질들이

모두 발현된다는 증거도 없어서 GABA에 이한 신호가 암세포에 직접적으로 영향을 줄 것이

라는 가정에 모순이 있어왔다. GABRP에 발현에 따라 invasion혹은 migration이 변화하는 것

이 GABA receptor와 관련이 있는 지 여부를 확인하기 위하여 GABRP가 없는 세포와 발현

한 세포 각각에서 GABA를 처리하였는데, GABA를 처리하지 않은 세포와 invasion혹은

migration에 아무런 차이가 없었다. 이러한 결과는 GABRP 발현에 따른 invasion과

migration의 변화가 GABA와는 무관하리라는 것을 시사하는 것이다. 이러한 결과는 췌장암의

성장이 GABA와 GABRP를 통해 일어난다는 Takehara등이 보고한 결과(2007)와도 차이가 있

다는 것을 알 수 있다. Takehara등의 논문에서는 GABA를 처리하면 암세포의 성장이 촉진된

다고 보고하였는데, 삼중음성유방암에서는 GABA를 처리하여도 암세포의 성장에도 변화가

없었으며, invasion이나 migration과도 아무런 관련성을 보이지 않았다. 다만 GABRP를 발현

시켰을 때 invaion과 migration이 감소하는 효과를 보였다. 따라서 삼중음성유방암에서는

- 28 -

GABA와 무관하게 GABRP의 발현여부가 invasion이나 migration과 관련이 있다고 할 수 있

다.

- 한편 GABA에 의해 전달되는 신호를 GABRP가 세포내로 전달하는데 그 하위 신호에는

calcium이 관여되어 있다는 것이 잘 알려져 있다. GABA에 의한 신호전달이 아닐 경우에도

GABRP가 calcium level에 영향을 줄 수 있을 것으로 생각하여 GABRP의 발현에 따른 세포

내 calcium level을 측정하였는데, GABRP가 발현된 세포에서 유의하게 세포내 calcium level

이 감소되어 있다는 것을 확인하였다. 이로서 삼중음성 유방암세포에서 GABRP가 GABA와

는 무관하게 세포내 calcium level을 조절하는데 관여한다는 것을 알 수 있었고, 이러한

calcium의 변화와 migration 혹은 invasion의 변화와 관련이 있을 것이라고 생각하게 되었다.

-또한 GABRP의 발현이 EMT pathway와 관련성이 있는 지 여부를 확인하기 위하여 E-cadherin

과 vimentin의 발현정도 변화를 확인하였는데, GABRP가 발현된 세포에서 E-cadherin이 증

가되어 있었고, vimentin은 감소되어 있어서 GABRP발현에 따른 invasion과 migration의 감

소라는 사실과 부합하였다. 현재 E-cadherin과 vimentin의 발현변화가 GABRP에 의한

calcium의 변화에 의한 것인지 아니면 calcium과는 독립적인 변화인지 확인할 수 없지만,

GABRP의 발현이 migration과 invasion을 감소시키는 방향으로 세포내 calcium level과 EMT

pathway를 조절한다는 것을 알 수 있었다. 이러한 GABRP와 세포내 calcium혹은 EMT관련

사실은 본 연구에서 처음 밝히게 된 내용으로 현재 GABRP에 의한 calcium의 변화가 세포내

어떠한 channel과 관련이 되어 있는지에 대해 연구하고 있다. 또한 GABRP의 발현한 세포가

mouse lung metastasis model에서 발현되지 않은 세포와 metastasis정도에 차이가 있는지에

관한 연구도 진행 중에 있다.

1) 유방암 subgroup별로 암발생과 관련있는 SNP 발굴: HER2, ER, PR 여부에 따른 비교

¡ 2003년부터 2007년까지 유방암으로 진단받고 수술/치료를 받은 환자 중 조직학적으로 확진되고 IHC가 판독 가능하면서 DNA가 유용한 여성 유방암 환자 1,026 명과 조직 검사를 통해 암이 발견되지 않은 대조군 중 연령을 매칭한 392 명을 대상으로 함 (Table 4).

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Characteristics Control (N=392)

Case (N=1026) p value1

Continuous variable Age at diagnosis, mean (SD), y 46.0(0.5) 46.8(0.3) 0.155 Age at menarche, mean (SD), y 14.6(0.1) 14.4(0.1) 0.039 Age at first parturition, mean (SD), y 25.4(0.2) 26.3(0.1) <.0001BMI, mean (SD), kg/m2 22.6(0.2) 23.1(0.1) 0.008

<18.5 22(5.6) 36(3.5) - 18.5 - 22.9 218(55.6) 528(51.4) - 23-24.9 76(19.3) 213(20.7) - ≥25 76(19.3) 249(24.2) -

Categorical variableMenopausal status, no (%)

Premenopausal 211(60.1) 706(70.0)Postmenopausal 140(39.9) 302(30.0) 0.0006

Oral contraceptive, no (%)no 333(86.1) 918(92.6)yes 54(14.0) 73(7.4) 0.0001

Hormone replacement therapy, (%)no 342(89.5) 915(92.6)yes 40(10.5) 73(7.4) 0.063

Breastfeeding status, N(%)no 106(27.6) 289(29.4)yes 278(72.4) 694(70.6) 0.51

Tumor size, cm, no (%)≤ 2 614(59.9)> 2 411(40.1)

Node status, no (%)N0 635(62.3)N1 + N2 + N3 384(37.7)

Stage, no (%)stage 0 +Ⅰ 453(44.5)stage Ⅱa + stage Ⅱb 416(40.9)stage Ⅲa + Ⅲb + Ⅲc + Ⅳ 　 149(14.6) 　

Table 4. Characteristics of the subjects in the study and distribution of risk factors

p value1:Control vs Case. t test for continuous variable and χ2 for categorical variable

¡ 384 SNPs 중에서 353개의 SNPs가 실험분석이 완료되었고, 이를 이용하여 유방암 발생과의 관련성을 분석함 (Table 5-1~5-7). 또한 유방암환자들의 호르몬 양성 여부에 따라 subgroup 분석을 시행함.

¡ 전체 유방암환자에서 암의 발생과 관련이 있는 SNPs을 Table 6-1~6-6에 제시하였고, 각 호르몬 수용체 아형에 따른 분석 결과는 Table 7-1~7-6 (Luminal A), Table 8-1~8-6 (Luminal B), Table 9-1~9-6 (HER2 over-expression), Table 10-1~10-6 (triple negative)에 제시함.

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¡ Gene-based analysis에서 global p value를 구한 결과, IGF1R가 가장 유의한 유전자로 분석됨(p=0.0003). 이 외에도 MAP2K2, ECHDC1, MAP2K1 등이 유의함 (Table 11).

¡ 특히 IGF1, IRS2, IGF1R 유전자는 삼중음성 유방암환자의 발생과 의미있는 관련성을 보임 (p trend = <0.05). IRS2 (4 SNPs)와 IGF1R (23 SNPs)는 BMI와의 상호작용이 있는 것으로 나타남 (P for interaction= <0.05). 이 결과를 통해 이들 유전적 다형성이 비만과의 상호작용을 통해 삼중음성 유방암의 발생에 기여할 것으로 생각됨.

¡ 51 개의 IGF1R SNPs 중에서 3개의 intron에 위치하는 SNPs (rs8032477, rs11635251, and rs12916884)가 유방암의 발생과 유의한 관련성을 보임 (OR(CI 95%) for homozygous genotype (variant genotype): 0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)).

¡ LD 분석을 통해 51 개 IGF1R SNPs를 이용해 분석해보면 7개의 haplotype block이 나왔고 (Figure 5-1~5-4), 그 중에서 하나의 haplotype block (rs4966007, rs8028620, rs4966009, rs8027457, rs4966012, rs1574213, rs11630479)이 유방암 발생과 유의한 관련성이 나타남 (Table 12-1~12-6).

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Table 5-1. Genotype frequency of SNPs　　 Control 　 Cases

Major Hetero Minor Major Hetero MinorGene rs # *N(%) 　 *N(%)

MTHFR rs1801131 256(65.3) 120(30.6) 16(4.1) 681(66.5) 309(30.2) 34(3.3)RIZ1 or PRDM2 rs2235515 128(32.7) 190(48.5) 74(18.9) 341(33.3) 508(49.6) 176(17.2)HSD11B1 rs4393158 161(41.2) 181(46.3) 49(12.5) 440(43.0) 458(44.7) 126(12.3)HSD11B1 rs17317033 387(98.7) 5(1.3) 0(0.0) 995(97.3) 28(2.7) 0(0.0)HSD11B1 rs2235543 143(36.5) 186(47.5) 63(16.1) 403(39.3) 481(46.9) 141(13.8)HSD11B1 rs11807619 259(66.1) 119(30.4) 14(3.6) 710(69.3) 284(27.7) 30(2.9)HSD11B1 rs932335 267(68.6) 111(28.5) 11(2.8) 738(72.4) 262(25.7) 20(2.0)2p(19150424) rs4666451 366(93.4) 26(6.6) 0(0.0) 962(94.0) 60(5.9) 1(0.1)CYP1B1 rs1800440 390(99.5) 2(0.5) 0(0.0) 1011(99.0) 10(1.0) 0(0.0)CYP1B1 rs1056836 313(79.9) 77(19.6) 2(0.5) 780(76.1) 231(22.5) 14(1.4)ITGA6 rs17664 293(75.1) 87(22.3) 10(2.6) 759(74.2) 238(23.3) 26(2.5)ITGAv rs11902171 332(84.7) 58(14.8) 2(0.5) 899(87.7) 118(11.5) 8(0.8)BARD1 rs6759222 333(85.6) 53(13.6) 3(0.8) 870(85.1) 143(14.0) 9(0.9)BARD1 rs4673896 163(41.6) 170(43.4) 59(15.1) 428(41.8) 461(45.0) 135(13.2)BARD1 rs6717301 111(28.5) 190(48.7) 89(22.8) 293(28.6) 527(51.4) 205(20.0)BARD1 rs2229571 194(49.9) 145(37.3) 50(12.9) 482(47.2) 439(43.0) 100(9.8)BARD1 rs3768704 121(31.0) 186(47.7) 83(21.3) 320(31.3) 520(50.8) 184(18.0)BARD1 rs7591615 354(90.8) 35(9.0) 1(0.3) 933(91.4) 83(8.1) 5(0.5)BARD1 rs6435862 284(72.5) 100(25.5) 8(2.0) 708(69.1) 289(28.2) 28(2.7)2q35 rs13387042 319(81.4) 69(17.6) 4(1.0) 837(81.7) 177(17.3) 11(1.1)FGFR2 rs12505080 122(31.1) 188(48.0) 82(20.9) 274(26.9) 545(53.4) 201(19.7)FGFR2 rs7696175 292(74.5) 94(24.0) 6(1.5) 765(74.9) 234(22.9) 22(2.2)KIT rs2237038 121(31.1) 202(51.9) 66(17.0) 348(34.0) 520(50.8) 156(15.2)KIT rs981959 120(31.0) 201(51.9) 66(17.1) 340(34.0) 512(51.2) 149(14.9)KIT rs2237034 233(59.4) 136(34.7) 23(5.9) 641(62.5) 332(32.4) 52(5.1)KIT rs2237032 201(51.5) 157(40.3) 32(8.2) 553(54.8) 386(38.2) 71(7.0)KIT rs2237023 152(38.9) 195(49.9) 44(11.3) 381(37.2) 502(49.0) 142(13.9)KIT rs6810872 152(38.8) 196(50.0) 44(11.2) 382(37.5) 499(48.9) 139(13.6)KIT rs3134884 238(60.7) 138(35.2) 16(4.1) 588(57.5) 389(38.0) 46(4.5)KIT rs3111800 99(25.3) 211(53.8) 82(20.9) 247(24.1) 530(51.8) 247(24.1)KIT rs2237018 217(55.4) 146(37.2) 29(7.4) 554(54.2) 399(39.0) 70(6.8)KIT rs6843170 221(56.4) 143(36.5) 28(7.1) 560(54.6) 397(38.7) 68(6.6)KDR rs17709898 226(57.7) 141(36.0) 25(6.4) 533(52.1) 423(41.4) 67(6.6)KDR rs12505758 236(60.2) 132(33.7) 24(6.1) 640(62.5) 348(34.0) 36(3.5)KDR rs2168945 168(42.9) 170(43.4) 54(13.8) 429(41.9) 466(45.6) 128(12.5)KDR rs13136007 144(36.8) 179(45.8) 68(17.4) 326(32.7) 489(49.1) 181(18.2)KDR rs11732292 169(43.1) 170(43.4) 53(13.5) 433(42.3) 465(45.5) 125(12.2)KDR rs1870377 143(36.5) 179(45.7) 70(17.9) 327(31.9) 512(50.0) 186(18.2)KDR rs7673274 227(58.5) 134(34.5) 27(7.0) 611(60.0) 359(35.3) 48(4.7)KDR rs11133360 156(39.8) 176(44.9) 60(15.3) 372(36.4) 488(47.7) 163(15.9)STE or SULT1E1 rs3775775 346(88.5) 43(11.0) 2(0.5) 883(86.7) 126(12.4) 10(1.0)STE or SULT1E1 rs1881668 173(44.1) 168(42.9) 51(13.0) 377(36.8) 491(48.0) 156(15.2)ADH1B rs1042026 252(64.3) 129(32.9) 11(2.8) 689(67.2) 304(29.7) 32(3.1)5p12 rs4415084 116(29.7) 182(46.6) 93(23.8) 334(32.7) 499(48.9) 188(18.4)MRPS30 rs10941679 117(29.9) 189(48.2) 86(21.9) 274(26.8) 494(48.3) 255(24.9)5p14 rs7703618 175(44.6) 175(44.6) 42(10.7) 493(48.1) 415(40.5) 117(11.4)5p15 rs10035564 117(29.9) 194(49.6) 80(20.5) 306(29.9) 515(50.3) 203(19.8)5p(45321475bp) rs981782 145(37.0) 187(47.7) 60(15.3) 377(36.8) 477(46.5) 171(16.7)52454339bp rs30099 127(32.4) 209(53.3) 56(14.3) 355(34.7) 496(48.4) 173(16.9)MAP3K1 rs889312 115(29.3) 195(49.7) 82(20.9) 319(31.2) 506(49.5) 198(19.4)DHFR rs1677666 378(96.4) 14(3.6) 0(0.0) 980(95.6) 45(4.4) 0(0.0)APC rs11954856 258(66.0) 120(30.7) 13(3.3) 721(70.3) 272(26.5) 32(3.1)APC rs11241183 192(49.1) 164(41.9) 35(9.0) 527(51.6) 410(40.1) 85(8.3)APC rs2439591 252(64.3) 126(32.1) 14(3.6) 702(68.6) 286(27.9) 36(3.5)*Frequency of allels among cases and controls

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Table 5-2. Genotype frequency of SNPs　　 Control Cases

Major Hetero Minor Major Hetero MinorGene rs # 　*N(%) *N(%)

APC s2431512 187(47.8) 167(42.7) 37(9.5) 520(50.7) 415(40.5) 90(8.8)APC rs2431238 322(82.6) 62(15.9) 6(1.5) 840(82.1) 169(16.5) 14(1.4)APC rs501250 327(83.4) 60(15.3) 5(1.3) 857(83.7) 153(14.9) 14(1.4)APC rs454886 185(47.2) 170(43.4) 37(9.4) 489(47.7) 429(41.9) 107(10.4)APC rs2229992 208(53.1) 153(39.0) 31(7.9) 563(54.9) 387(37.8) 75(7.3)APC rs41116 210(53.6) 154(39.3) 28(7.1) 574(56.1) 381(37.2) 69(6.7)APC rs448475 208(53.2) 155(39.6) 28(7.2) 571(55.8) 381(37.2) 72(7.0)CDKN1A rs3176336 217(55.4) 142(36.2) 33(8.4) 523(51.1) 430(42.0) 71(6.9)CDKN1A rs1801270 101(25.8) 203(51.9) 87(22.3) 311(30.4) 497(48.5) 216(21.1)CCND3 rs2479717 334(85.2) 58(14.8) 0(0.0) 870(85.4) 141(13.8) 8(0.8)LSP1 rs381798 131(33.4) 191(48.7) 70(17.9) 350(34.2) 508(49.6) 167(16.3)ECHDC1 rs2180341 203(51.8) 161(41.1) 28(7.1) 519(50.7) 411(40.1) 94(9.2)ECHDC1 rs6569479 202(51.7) 161(41.2) 28(7.2) 519(50.7) 411(40.1) 94(9.2)ECHDC1 rs6569480 203(51.9) 160(40.9) 28(7.2) 520(50.7) 411(40.1) 94(9.2)ECHDC1 rs7776136 202(51.8) 160(41.0) 28(7.2) 516(50.7) 407(40.0) 94(9.2)ESR1 rs851984 305(77.8) 77(19.6) 10(2.6) 796(77.7) 215(21.0) 13(1.3)ESR1 rs851982 303(77.3) 79(20.2) 10(2.6) 796(77.7) 215(21.0) 14(1.4)ESR1 rs2881766 143(36.5) 183(46.7) 66(16.8) 316(30.9) 537(52.4) 171(16.7)ESR1 rs2077647 172(43.9) 167(42.6) 53(13.5) 396(38.6) 471(46.0) 158(15.4)ESR1 rs9322331 377(96.2) 15(3.8) 0(0.0) 973(95.0) 50(4.9) 1(0.1)ESR1 rs712221 129(32.9) 188(48.0) 75(19.1) 309(30.2) 495(48.3) 221(21.6)ESR1 rs1801132 95(24.2) 197(50.3) 100(25.5) 281(27.4) 501(48.9) 242(23.6)ESR1 rs3020314 263(67.1) 117(29.9) 12(3.1) 667(65.1) 326(31.8) 31(3.0)ESR1 rs3020377 262(66.8) 117(29.9) 13(3.3) 664(64.8) 329(32.1) 31(3.0)ESR1 rs3020390 166(42.4) 181(46.2) 45(11.5) 453(44.2) 453(44.2) 119(11.6)ESR1 rs3020317 116(29.6) 200(51.0) 76(19.4) 328(32.0) 478(46.6) 219(21.4)ESR1 rs3020394 158(40.3) 183(46.7) 51(13.0) 430(42.0) 466(45.5) 129(12.6)ESR1 rs3020396 150(38.6) 185(47.6) 54(13.9) 417(40.7) 473(46.2) 134(13.1)ESR1 rs3020401 151(38.6) 186(47.6) 54(13.8) 416(40.6) 474(46.3) 134(13.1)ESR1 rs1884051 108(27.6) 194(49.5) 90(23.0) 302(29.5) 501(48.9) 222(21.7)ESR1 rs1884054 198(50.5) 164(41.8) 30(7.7) 526(51.4) 414(40.4) 84(8.2)ESR1 rs3020405 197(50.4) 162(41.4) 32(8.2) 524(51.1) 415(40.5) 86(8.4)ESR1 rs726282 138(35.2) 191(48.7) 63(16.1) 390(38.1) 477(46.5) 158(15.4)ESR1 rs3020407 184(47.1) 172(44.0) 35(9.0) 487(47.5) 432(42.2) 106(10.3)ESR1 rs6905370 115(29.3) 200(51.0) 77(19.6) 308(30.1) 513(50.1) 203(19.8)ESR1 rs926778 152(39.0) 172(44.1) 66(16.9) 326(31.9) 537(52.6) 158(15.5)ESR1 rs3020366 129(32.9) 182(46.4) 81(20.7) 320(31.3) 546(53.3) 158(15.4)ESR1 rs2273206 187(47.7) 160(40.8) 45(11.5) 417(40.9) 494(48.4) 109(10.7)ESR1 rs750686 114(29.1) 191(48.7) 87(22.2) 301(29.4) 540(52.7) 183(17.9)ESR1 rs2228480 231(58.9) 144(36.7) 17(4.3) 661(64.7) 335(32.8) 26(2.5)ESR1 rs3798577 131(33.4) 203(51.8) 58(14.8) 427(41.7) 450(43.9) 148(14.4)ESR1 rs910416 144(37.0) 186(47.8) 59(15.2) 422(41.3) 479(46.9) 121(11.8)IGFBP3 rs2854744 246(63.1) 111(28.5) 33(8.5) 610(60.2) 355(35.0) 48(4.7)EGFR rs11770506 189(48.2) 159(40.6) 44(11.2) 524(51.1) 415(40.5) 86(8.4)EGFR rs4947974 171(43.6) 179(45.7) 42(10.7) 459(44.8) 466(45.5) 99(9.7)EGFR rs2110290 180(45.9) 173(44.1) 39(10.0) 469(45.9) 465(45.5) 88(8.6)EGFR rs12667668 182(46.4) 165(42.1) 45(11.5) 446(43.6) 481(47.0) 96(9.4)EGFR rs12718945 180(46.0) 167(42.7) 44(11.3) 443(43.2) 482(47.0) 100(9.8)EGFR rs6593207 207(52.8) 149(38.0) 36(9.2) 482(47.1) 468(45.7) 74(7.2)EGFR rs2072454 169(43.1) 170(43.4) 53(13.5) 405(39.5) 504(49.2) 116(11.3)EGFR rs11536635 141(36.1) 186(47.6) 64(16.4) 344(33.6) 520(50.8) 159(15.5)EGFR rs11977388 187(47.7) 160(40.8) 45(11.5) 445(43.5) 491(48.0) 86(8.4)EGFR rs10228436 155(39.5) 172(43.9) 65(16.6) 357(35.0) 519(50.9) 144(14.1)*Frequency of allels among cases and controls

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Major Hetero Minor Major Hetero MinorGene rs # *　N(%) *N(%)

ABCB1 rs1045642 168(43.3) 171(44.1) 49(12.6) 420(41.0) 475(46.4) 129(12.6)ABCB1 rs7787082 123(31.7) 191(49.2) 74(19.1) 303(29.7) 514(50.3) 205(20.1)ABCB1 rs2091766 151(38.6) 179(45.8) 61(15.6) 440(42.9) 459(44.8) 126(12.3)ABCB1 rs1128503 134(34.2) 186(47.5) 72(18.4) 380(37.2) 492(48.1) 151(14.8)ABCB1 rs1922241 153(39.0) 181(46.2) 58(14.8) 442(43.1) 465(45.4) 118(11.5)ABCB1 rs868755 142(36.2) 200(51.0) 50(12.8) 382(37.3) 491(47.9) 152(14.8)ABCB1 rs2520464 135(34.5) 184(47.1) 72(18.4) 386(37.7) 491(48.0) 146(14.3)ABCB1 rs1202184 166(42.8) 164(42.3) 58(15.0) 451(44.4) 459(45.1) 107(10.5)ABCB1 rs12535512 117(29.9) 203(51.8) 72(18.4) 309(30.2) 525(51.3) 189(18.5)ABCB1 rs9282564 391(100.0) 0(0.0) 0(0.0) 1023(99.9) 1(0.1) 0(0.0)ABCB1 rs12720464 225(57.4) 149(38.0) 18(4.6) 530(51.8) 430(42.0) 63(6.2)ABCB1 rs1978095 227(57.9) 146(37.2) 19(4.9) 529(51.8) 429(42.0) 64(6.3)CDK6 rs3757823 85(21.7) 187(47.7) 120(30.6) 265(25.9) 531(51.9) 228(22.3)Q129R rs662 152(38.8) 189(48.2) 51(13.0) 448(43.7) 481(46.9) 96(9.4)L55M rs854560 342(87.2) 49(12.5) 1(0.3) 903(88.2) 116(11.3) 5(0.5)FGFR2 rs17157903 229(58.4) 142(36.2) 21(5.4) 594(58.0) 364(35.6) 66(6.5)MET rs2237710 147(37.9) 177(45.6) 64(16.5) 381(37.2) 496(48.5) 146(14.3)MET rs2299437 177(45.2) 168(42.9) 47(12.0) 458(44.8) 454(44.4) 111(10.9)MET rs10248537 177(45.2) 168(42.9) 47(12.0) 456(44.7) 452(44.3) 112(11.0)MET rs38855 150(38.4) 175(44.8) 66(16.9) 347(33.9) 490(47.9) 186(18.2)MET rs38858 151(38.5) 175(44.6) 66(16.8) 346(33.8) 492(48.1) 186(18.2)MET rs13223756 216(55.1) 141(36.0) 35(8.9) 549(53.7) 403(39.4) 70(6.9)MET rs2299440 216(55.1) 141(36.0) 35(8.9) 551(53.8) 404(39.4) 70(6.8)MET rs183642 108(27.6) 175(44.6) 109(27.8) 253(24.7) 540(52.7) 231(22.6)MET rs41736 109(27.8) 174(44.4) 109(27.8) 253(24.7) 540(52.7) 232(22.6)MET rs41739 109(28.1) 171(44.1) 108(27.8) 252(24.7) 538(52.8) 229(22.5)TBXAS1 rs6971207 182(47.0) 164(42.4) 41(10.6) 439(43.0) 464(45.5) 118(11.6)XRCC2 rs3218536 392(100.0) 0(0.0) 0(0.0) 1023(99.8) 2(0.2) 0(0.0)FGFR1 rs2304000 170(43.5) 176(45.0) 45(11.5) 420(41.1) 475(46.5) 126(12.3)FGFR1 rs4647907 170(43.6) 176(45.1) 44(11.3) 416(41.2) 467(46.2) 128(12.7)FGFR1 rs2956724 188(48.1) 174(44.5) 29(7.4) 511(50.0) 434(42.4) 78(7.6)FGFR1 rs2978073 185(47.3) 177(45.3) 29(7.4) 510(49.9) 431(42.1) 82(8.0)FGFR1 rs6983315 159(40.6) 185(47.2) 48(12.2) 448(43.7) 437(42.6) 140(13.7)FGFR1 rs6987534 166(42.5) 179(45.8) 46(11.8) 462(45.1) 433(42.3) 129(12.6)NBS1 rs9995 149(38.0) 170(43.4) 73(18.6) 390(38.1) 484(47.3) 149(14.6)NBS1 or NBN rs1805787 386(98.5) 6(1.5) 0(0.0) 1015(99.1) 9(0.9) 0(0.0)8q24 rs13281615 122(31.1) 203(51.8) 67(17.1) 338(33.0) 487(47.5) 200(19.5)MYC rs3891248 125(31.9) 203(51.8) 64(16.3) 329(32.1) 513(50.1) 183(17.9)CDKN2A rs3731239 277(70.8) 102(26.1) 12(3.1) 771(75.3) 235(23.0) 18(1.8)MCS5A6 rs2182317 262(66.8) 115(29.3) 15(3.8) 695(67.8) 298(29.1) 32(3.1)EHMT1 rs4634736 390(99.5) 2(0.5) 0(0.0) 1019(99.4) 6(0.6) 0(0.0)FLJ45983 rs1149901 337(86.4) 50(12.8) 3(0.8) 905(88.6) 110(10.8) 7(0.7)GATA3 rs570613 139(35.6) 198(50.6) 54(13.8) 471(46.0) 434(42.3) 120(11.7)GATA3 rs422628 340(87.0) 50(12.8) 1(0.3) 909(88.8) 109(10.6) 6(0.6)FGFR2 rs11200014 211(53.8) 150(38.3) 31(7.9) 523(51.0) 422(41.2) 80(7.8)FGFR2 rs2981579 129(33.0) 194(49.6) 68(17.4) 305(29.8) 507(49.6) 211(20.6)FGFR2 rs1078806 214(54.6) 147(37.5) 31(7.9) 529(51.8) 416(40.7) 76(7.4)FGFR2 rs1219648 156(39.9) 180(46.0) 55(14.1) 368(36.0) 493(48.2) 162(15.8)FGFR2 rs2420946 163(41.6) 172(43.9) 57(14.5) 370(36.1) 491(47.9) 164(16.0)FGFR2 rs2981582 204(52.0) 147(37.5) 41(10.5) 470(45.9) 456(44.5) 98(9.6)FGFR2 rs10510126 356(90.8) 36(9.2) 0(0.0) 917(89.6) 105(10.3) 2(0.2)LSP1 rs661348 153(39.2) 174(44.6) 63(16.2) 357(35.6) 486(48.4) 161(16.0)LSP1 rs3817198 283(72.2) 100(25.5) 9(2.3) 744(72.6) 256(25.0) 25(2.4)*Frequency of allels among cases and controls

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H19 rs2107425 101(25.8) 203(51.9) 87(22.3) 309(30.2) 520(50.7) 196(19.1)CCND1 rs3212891 289(73.9) 97(24.8) 5(1.3) 775(75.8) 230(22.5) 17(1.7)CCND1 rs678653 296(75.5) 91(23.2) 5(1.3) 785(76.7) 222(21.7) 17(1.7)NUMA1 rs3750913 342(87.2) 48(12.2) 2(0.5) 913(89.1) 109(10.6) 3(0.3)PGR rs500760 255(65.1) 129(32.9) 8(2.0) 673(65.9) 321(31.4) 28(2.7)PGR rs511298 267(68.1) 118(30.1) 7(1.8) 699(68.6) 296(29.1) 24(2.4)PGR rs1042839 390(99.7) 1(0.3) 0(0.0) 1016(99.1) 9(0.9) 0(0.0)PGR rs492457 392(100.0) 0(0.0) 0(0.0) 1022(100.0) 0(0.0) 0(0.0)PGR rs1042838 391(99.7) 1(0.3) 0(0.0) 1013(99.0) 10(1.0) 0(0.0)PGR rs660149 380(96.9) 12(3.1) 0(0.0) 992(97.0) 31(3.0) 0(0.0)PGR rs2020876 384(98.0) 8(2.0) 0(0.0) 1007(98.2) 18(1.8) 0(0.0)PGR rs7116336 261(66.6) 120(30.6) 11(2.8) 671(65.5) 322(31.4) 32(3.1)PGR rs578938 386(100.0) 0(0.0) 0(0.0) 1002(100.0) 0(0.0) 0(0.0)PGR rs11571171 277(70.8) 110(28.1) 4(1.0) 720(70.5) 279(27.3) 22(2.2)PGR rs566351 274(69.9) 109(27.8) 9(2.3) 693(67.7) 309(30.2) 22(2.2)PGR rs506487 390(99.5) 2(0.5) 0(0.0) 1021(99.6) 4(0.4) 0(0.0)PGR rs10895068 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)PGR rs518162 380(96.9) 11(2.8) 1(0.3) 988(96.4) 37(3.6) 0(0.0)MMP8 rs1892886 332(84.7) 55(14.0) 5(1.3) 851(83.0) 166(16.2) 8(0.8)ATM rs1800054 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)ATM rs1801516 392(100.0) 0(0.0) 0(0.0) 1024(100.0) 0(0.0) 0(0.0)CDKN1B rs34330 132(33.8) 183(46.8) 76(19.4) 314(31.0) 474(46.8) 226(22.3)IGF1 rs2946834 113(28.8) 188(48.0) 91(23.2) 320(31.3) 495(48.3) 209(20.4)IGF1 rs5742714 271(69.3) 106(27.1) 14(3.6) 713(69.7) 270(26.4) 40(3.9)IGF1 rs6214 99(25.3) 187(47.7) 106(27.0) 288(28.1) 476(46.4) 261(25.5)IGF1 rs1520220 130(33.2) 180(45.9) 82(20.9) 346(33.8) 499(48.7) 179(17.5)IGF1 rs10745940 130(33.3) 180(46.0) 81(20.7) 347(33.9) 498(48.7) 178(17.4)IGF1 rs5742694 272(69.6) 105(26.9) 14(3.6) 710(69.6) 272(26.7) 38(3.7)IGF1 rs978458 130(33.2) 179(45.7) 83(21.2) 345(33.7) 498(48.6) 181(17.7)IGF1 rs5742667 128(32.7) 179(45.7) 85(21.7) 341(33.3) 500(48.8) 184(18.0)IGF1 rs2373721 270(68.9) 109(27.8) 13(3.3) 711(69.4) 273(26.6) 41(4.0)IGF1 rs7136446 270(68.9) 109(27.8) 13(3.3) 706(69.1) 273(26.7) 43(4.2)IGF1 rs2033178 392(100.0) 0(0.0) 0(0.0) 1024(100.0) 0(0.0) 0(0.0)IGF1 rs9989002 277(70.7) 105(26.8) 10(2.6) 752(73.4) 236(23.0) 37(3.6)IGF1 rs5742632 132(34.2) 174(45.1) 80(20.7) 365(35.9) 497(48.9) 155(15.2)IGF1 rs2195240 134(34.3) 176(45.0) 81(20.7) 363(35.9) 490(48.5) 157(15.5)IGF1 rs5742629 134(34.2) 177(45.2) 81(20.7) 365(35.6) 501(48.9) 159(15.5)IGF1 rs7956547 282(71.9) 100(25.5) 10(2.6) 759(74.1) 238(23.2) 28(2.7)IGF1 rs4764698 207(52.8) 151(38.5) 34(8.7) 569(55.5) 387(37.8) 69(6.7)IGF1 rs10778176 133(34.1) 174(44.6) 83(21.3) 360(35.2) 506(49.5) 157(15.4)IGF1 rs1019731 392(100.0) 0(0.0) 0(0.0) 1018(99.5) 5(0.5) 0(0.0)IGF1 rs2162679 159(40.6) 183(46.7) 50(12.8) 436(42.6) 469(45.9) 118(11.5)IGF1 rs35765 361(92.1) 28(7.1) 3(0.8) 918(89.7) 105(10.3) 1(0.1)IGF1 rs7965399 200(51.0) 163(41.6) 29(7.4) 535(52.2) 415(40.5) 75(7.3)IGF1 rs855211 179(45.7) 175(44.6) 38(9.7) 471(46.0) 453(44.3) 99(9.7)BRCA2 rs144848 211(53.8) 163(41.6) 18(4.6) 561(54.8) 393(38.4) 70(6.8)BRCA2 rs4942485 372(94.9) 20(5.1) 0(0.0) 978(95.5) 44(4.3) 2(0.2)RB1 rs2854344 392(100.0) 0(0.0) 0(0.0) 1024(100.0) 0(0.0) 0(0.0)LIG4 rs1805386 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)IRS2 rs9515118 219(55.9) 140(35.7) 33(8.4) 549(53.6) 407(39.7) 69(6.7)IRS2 rs4773082 206(52.6) 160(40.8) 26(6.6) 551(53.8) 415(40.5) 59(5.8)IRS2 rs2289046 116(29.6) 195(49.7) 81(20.7) 291(28.4) 509(49.7) 225(22.0)IRS2 rs754204 179(45.7) 184(46.9) 29(7.4) 493(48.1) 442(43.1) 90(8.8)*Frequency of allels among cases and controls

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IRS2 rs7987237 231(59.1) 135(34.5) 25(6.4) 596(58.2) 375(36.6) 54(5.3)IRS2 rs12584136 359(91.6) 33(8.4) 0(0.0) 933(91.4) 85(8.3) 3(0.3)IRS2 rs9559648 238(60.7) 140(35.7) 14(3.6) 643(62.9) 338(33.0) 42(4.1)IRS2 rs9559654 256(65.3) 125(31.9) 11(2.8) 663(64.7) 325(31.7) 37(3.6)IRS2 rs7997595 216(55.2) 143(36.6) 32(8.2) 572(55.9) 389(38.0) 63(6.2)IRS2 rs7981705 368(93.9) 23(5.9) 1(0.3) 973(95.0) 51(5.0) 0(0.0)IRS2 rs4773092 116(29.7) 183(46.9) 91(23.3) 289(28.4) 514(50.5) 215(21.1)ESR2 rs1255998 127(32.4) 187(47.7) 78(19.9) 298(29.1) 513(50.1) 214(20.9)ESR2 rs8018687 325(83.6) 61(15.7) 3(0.8) 854(83.8) 159(15.6) 6(0.6)ESR2 rs928554 158(40.3) 180(45.9) 54(13.8) 424(41.4) 468(45.7) 133(13.0)ESR2 rs1152579 160(40.8) 178(45.4) 54(13.8) 429(41.9) 466(45.5) 130(12.7)ESR2 rs1256049 203(51.8) 162(41.3) 27(6.9) 505(49.3) 432(42.2) 87(8.5)ESR2 rs1256030 153(39.0) 182(46.4) 57(14.5) 403(39.3) 480(46.8) 142(13.9)ESR2 rs1271572 147(38.0) 182(47.0) 58(15.0) 388(38.3) 484(47.7) 142(14.0)XRCC3 rs861539 361(92.3) 30(7.7) 0(0.0) 933(91.1) 89(8.7) 2(0.2)XRCC3 rs1799796 174(44.4) 173(44.1) 45(11.5) 487(47.5) 440(42.9) 98(9.6)XRCC3 rs1799794 105(26.8) 189(48.2) 98(25.0) 283(27.6) 503(49.1) 238(23.2)AKT1 rs2494744 166(42.4) 175(44.6) 51(13.0) 405(39.6) 471(46.1) 146(14.3)AKT1 rs2498787 154(39.3) 186(47.5) 52(13.3) 399(39.0) 470(45.9) 154(15.1)CYP20 rs4646 195(49.9) 158(40.4) 38(9.7) 512(51.0) 406(40.4) 87(8.7)CYP19 rs10046 111(28.3) 199(50.8) 82(20.9) 295(28.8) 504(49.3) 224(21.9)CYP21 rs727479 182(46.4) 168(42.9) 42(10.7) 507(49.5) 422(41.2) 95(9.3)MAP2K1 rs7174378 110(28.1) 198(50.5) 84(21.4) 305(29.8) 522(50.9) 198(19.3)MAP2K1 rs7181936 154(39.3) 183(46.7) 55(14.0) 393(38.3) 474(46.2) 158(15.4)MAP2K1 rs28620576 195(49.7) 166(42.4) 31(7.9) 495(48.3) 432(42.2) 98(9.6)MAP2K1 rs8039880 131(33.4) 190(48.5) 71(18.1) 372(36.3) 490(47.8) 163(15.9)CYP1A1 rs1048943 247(63.0) 129(32.9) 16(4.1) 586(57.2) 379(37.0) 60(5.9)IGF1R rs4966007 153(39.0) 178(45.4) 61(15.6) 370(36.1) 478(46.7) 176(17.2)IGF1R rs8028620 113(28.8) 185(47.2) 94(24.0) 276(27.0) 497(48.6) 250(24.4)IGF1R rs4966009 155(39.9) 176(45.2) 58(14.9) 374(37.0) 467(46.2) 169(16.7)IGF1R rs8027457 114(29.2) 183(46.8) 94(24.0) 276(26.9) 499(48.7) 250(24.4)IGF1R rs4966012 186(47.5) 173(44.1) 33(8.4) 509(49.7) 433(42.3) 82(8.0)IGF1R rs1574213 245(62.5) 136(34.7) 11(2.8) 639(62.3) 337(32.9) 49(4.8)IGF1R rs11630479 189(48.3) 170(43.5) 32(8.2) 517(50.6) 425(41.6) 80(7.8)IGF1R rs4966013 115(29.4) 191(48.9) 85(21.7) 293(28.6) 497(48.5) 234(22.9)IGF1R rs4966015 226(57.8) 148(37.9) 17(4.4) 617(60.2) 358(34.9) 50(4.9)IGF1R rs8032477 102(26.1) 193(49.4) 96(24.6) 287(28.1) 535(52.4) 200(19.6)IGF1R rs11634241 176(44.9) 177(45.2) 39(10.0) 490(47.8) 427(41.7) 108(10.5)IGF1R rs932071 232(59.2) 140(35.7) 20(5.1) 646(63.0) 333(32.5) 46(4.5)IGF1R rs875686 215(54.9) 152(38.8) 25(6.4) 602(58.9) 364(35.6) 57(5.6)IGF1R rs1567811 143(36.5) 189(48.2) 60(15.3) 387(37.8) 507(49.5) 131(12.8)IGF1R rs11632952 229(58.4) 142(36.2) 21(5.4) 633(61.8) 341(33.3) 51(5.0)IGF1R rs4966024 97(24.7) 204(52.0) 91(23.2) 267(26.1) 530(51.9) 225(22.0)IGF1R rs8041224 132(35.0) 179(47.5) 66(17.5) 389(38.0) 491(48.0) 144(14.1)IGF1R rs7175052 143(36.5) 180(45.9) 69(17.6) 405(39.6) 485(47.4) 134(13.1)IGF1R rs2137680 104(26.5) 189(48.2) 99(25.3) 275(26.9) 527(51.5) 221(21.6)IGF1R rs12439557 205(52.3) 149(38.0) 38(9.7) 563(55.0) 389(38.0) 72(7.0)IGF1R rs4966028 286(73.0) 96(24.5) 10(2.6) 753(73.5) 239(23.3) 33(3.2)IGF1R rs907806 283(72.8) 99(25.5) 7(1.8) 755(74.0) 236(23.1) 30(2.9)IGF1R rs8041953 277(70.7) 106(27.0) 9(2.3) 737(72.0) 256(25.0) 30(2.9)IGF1R rs2670501 133(33.9) 195(49.7) 64(16.3) 395(38.5) 468(45.7) 162(15.8)IGF1R rs4246340 117(29.9) 203(51.9) 71(18.2) 289(28.3) 503(49.2) 231(22.6)IGF1R rs2684777 131(33.4) 202(51.5) 59(15.1) 372(36.3) 484(47.2) 169(16.5)IGF1R rs8030950 234(59.7) 134(34.2) 24(6.1) 593(57.9) 378(36.9) 54(5.3)*Frequency of allels among cases and controls

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IGF1R rs12594847 156(40.3) 177(45.7) 54(14.0) 401(39.5) 468(46.1) 146(14.4)IGF1R rs2684781 156(39.8) 177(45.2) 59(15.1) 406(39.7) 466(45.5) 152(14.8)IGF1R rs1521481 227(58.1) 137(35.0) 27(6.9) 582(56.8) 388(37.9) 55(5.4)IGF1R rs4966035 107(27.3) 201(51.3) 84(21.4) 322(31.4) 462(45.1) 241(23.5)IGF1R rs4966036 143(36.5) 193(49.2) 56(14.3) 400(39.1) 469(45.8) 155(15.1)IGF1R rs7165875 107(27.3) 198(50.5) 87(22.2) 311(30.4) 459(44.9) 253(24.7)IGF1R rs3743259 102(26.0) 206(52.6) 84(21.4) 306(29.9) 461(45.0) 258(25.2)IGF1R rs3743260 292(74.5) 89(22.7) 11(2.8) 742(72.5) 255(24.9) 27(2.6)IGF1R rs2684810 208(53.1) 151(38.5) 33(8.4) 512(50.0) 434(42.4) 78(7.6)IGF1R rs4966039 259(66.1) 119(30.4) 14(3.6) 690(67.5) 303(29.7) 29(2.8)IGF1R rs2684805 132(33.7) 189(48.2) 71(18.1) 312(30.4) 512(50.0) 201(19.6)IGF1R rs2684803 181(46.2) 163(41.6) 48(12.2) 417(40.8) 482(47.2) 123(12.0)IGF1R rs1546713 180(45.9) 164(41.8) 48(12.2) 416(40.7) 485(47.4) 122(11.9)IGF1R rs7166558 178(45.4) 166(42.4) 48(12.2) 408(39.8) 492(48.0) 125(12.2)IGF1R rs2229765 180(46.2) 163(41.8) 47(12.1) 416(40.7) 481(47.1) 124(12.1)IGF1R rs11635251 177(45.2) 170(43.4) 45(11.5) 482(47.0) 462(45.1) 81(7.9)IGF1R rs8038056 197(50.3) 149(38.0) 46(11.7) 492(48.0) 454(44.3) 79(7.7)IGF1R rs12916884 178(45.4) 159(40.6) 55(14.0) 483(47.2) 460(44.9) 81(7.9)IGF1R rs7173377 193(49.4) 150(38.4) 48(12.3) 464(45.4) 451(44.1) 108(10.6)IGF1R rs7166565 187(47.7) 155(39.5) 50(12.8) 442(43.2) 466(45.6) 115(11.2)IGF1R rs939626 223(56.9) 136(34.7) 33(8.4) 596(58.2) 376(36.7) 52(5.1)IGF1R rs12437963 158(40.3) 180(45.9) 54(13.8) 382(37.3) 487(47.5) 156(15.2)IGF1R rs2684788 117(29.9) 193(49.4) 81(20.7) 307(30.0) 497(48.6) 219(21.4)IGF1R rs1815009 125(31.9) 183(46.7) 84(21.4) 307(30.0) 502(49.0) 216(21.1)A2BP1 rs7203563 250(63.9) 127(32.5) 14(3.6) 688(67.4) 300(29.4) 33(3.2)TNRC9/LOC643714 rs8051542 247(63.0) 131(33.4) 14(3.6) 594(58.0) 381(37.2) 49(4.8)TNRC9/LOC643714 rs12443621 160(40.9) 183(46.8) 48(12.3) 409(39.9) 481(47.0) 134(13.1)TNRC9 or TOX3 rs3803662 139(35.5) 192(49.0) 61(15.6) 444(43.4) 448(43.8) 131(12.8)ATP1B2 rs1641512 149(38.0) 178(45.4) 65(16.6) 398(38.9) 482(47.1) 144(14.1)TP53 rs9894946 366(93.4) 26(6.6) 0(0.0) 950(92.8) 74(7.2) 0(0.0)TP53 rs1614984 174(44.7) 167(42.9) 48(12.3) 494(48.6) 419(41.2) 103(10.1)TP53 rs1042522 147(37.9) 183(47.2) 58(15.0) 437(43.1) 448(44.1) 130(12.8)WDR79 rs2287499 212(54.1) 159(40.6) 21(5.4) 609(59.4) 366(35.7) 50(4.9)WDR79 rs17885803 321(82.1) 68(17.4) 2(0.5) 858(83.7) 157(15.3) 10(1.0)WDR79 rs2287498 213(54.3) 158(40.3) 21(5.4) 609(59.5) 364(35.6) 50(4.9)WDR79 rs17886268 391(99.7) 1(0.3) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)HER2 rs4252600 392(100.0) 0(0.0) 0(0.0) 1023(100.0) 0(0.0) 0(0.0)HER2 rs1565923 140(35.7) 195(49.7) 57(14.5) 327(31.9) 522(50.9) 176(17.2)HER2 rs4252610 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)ERBB rs1810132 141(36.0) 194(49.5) 57(14.5) 328(32.1) 521(50.9) 174(17.0)HER2 rs4252632 392(100.0) 0(0.0) 0(0.0) 1022(100.0) 0(0.0) 0(0.0)HER2 rs4252635 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)HER2 rs4252645 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)HER2 rs2172826 391(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)HER2 rs4252654 392(100.0) 0(0.0) 0(0.0) 1022(100.0) 0(0.0) 0(0.0)HER2 rs4252657 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)HER2 rs4252660 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)HER2 rs3809717 207(52.8) 157(40.1) 28(7.1) 530(52.0) 407(39.9) 83(8.1)ITGB3 rs3809865 244(62.2) 132(33.7) 16(4.1) 637(62.2) 340(33.2) 47(4.6)ITGA3 rs1062484 387(98.7) 5(1.3) 0(0.0) 1018(99.3) 7(0.7) 0(0.0)AXIN2 rs7210356 294(75.0) 86(21.9) 12(3.1) 760(74.2) 242(23.6) 22(2.2)AXIN2 rs4791171 159(40.6) 179(45.7) 54(13.8) 463(45.2) 447(43.6) 115(11.2)AXIN2 rs11079571 217(55.4) 145(37.0) 30(7.7) 517(50.4) 415(40.5) 93(9.1)*Frequency of allels among cases and controls

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AXIN2 rs3923087 162(41.3) 183(46.7) 47(12.0) 461(45.0) 447(43.7) 116(11.3)AXIN2 rs3923086 265(67.8) 116(29.7) 10(2.6) 735(71.9) 268(26.2) 20(2.0)GPX4 rs4807542 257(65.6) 116(29.6) 19(4.9) 674(65.9) 318(31.1) 31(3.0)MAP2K2 rs350916 170(43.4) 173(44.1) 49(12.5) 414(40.4) 496(48.4) 114(11.1)MAP2K2 rs350913 169(43.1) 169(43.1) 54(13.8) 398(38.9) 510(49.8) 116(11.3)MAP2K2 rs7258366 202(51.5) 152(38.8) 38(9.7) 447(43.6) 486(47.4) 92(9.0)MAP2K2 rs350894 144(36.8) 189(48.3) 58(14.8) 333(32.5) 535(52.2) 157(15.3)MAP2K2 rs12459484 168(43.1) 165(42.3) 57(14.6) 352(34.4) 520(50.8) 151(14.8)ICAM5 rs1056538 187(47.7) 169(43.1) 36(9.2) 478(46.6) 439(42.8) 108(10.5)CCNE1 rs997669 331(84.4) 57(14.5) 4(1.0) 842(82.2) 170(16.6) 13(1.3)XRCC1 rs25487 232(59.2) 143(36.5) 17(4.3) 556(54.3) 404(39.5) 64(6.3)DNMT3B rs406193 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)PTGIS rs6095541 329(83.9) 62(15.8) 1(0.3) 872(85.1) 145(14.2) 8(0.8)PTGIS rs6095543 276(70.4) 106(27.0) 10(2.6) 722(70.7) 272(26.6) 28(2.7)PTGIS rs693649 148(37.8) 181(46.2) 63(16.1) 382(37.3) 496(48.4) 146(14.3)AURKA rs8173 171(43.9) 183(46.9) 36(9.2) 423(41.4) 460(45.1) 138(13.5)AURKA rs10485805 223(57.0) 153(39.1) 15(3.8) 585(57.6) 371(36.5) 60(5.9)AURKA rs6024840 186(47.6) 162(41.4) 43(11.0) 470(45.9) 463(45.2) 91(8.9)AURKA rs911160 185(47.3) 163(41.7) 43(11.0) 470(45.9) 460(44.9) 95(9.3)AURKA rs2298016 173(44.4) 169(43.3) 48(12.3) 450(44.2) 459(45.1) 109(10.7)AURKA rs2273535 171(44.3) 167(43.3) 48(12.4) 444(43.7) 463(45.6) 109(10.7)STK15 rs732417 392(100.0) 0(0.0) 0(0.0) 1024(100.0) 0(0.0) 0(0.0)COMT rs4680 179(45.7) 188(48.0) 25(6.4) 529(51.8) 413(40.4) 80(7.8)CHEK2 rs9608698 223(56.9) 156(39.8) 13(3.3) 609(59.5) 359(35.1) 56(5.5)AR rs962458 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)AR rs6152 392(100.0) 0(0.0) 0(0.0) 1023(100.0) 0(0.0) 0(0.0)AR rs1204038 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)AR rs2361634 391(99.7) 1(0.3) 0(0.0) 1024(99.9) 1(0.1) 0(0.0)AR rs1337080 392(100.0) 0(0.0) 0(0.0) 1022(99.9) 1(0.1) 0(0.0)AR rs1337082 392(100.0) 0(0.0) 0(0.0) 1025(100.0) 0(0.0) 0(0.0)PHKA1 rs3012642 277(70.7) 105(26.8) 10(2.6) 722(70.6) 270(26.4) 31(3.0)*Frequency of allels among cases and controls

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　　 Overall (additive model)Hetero Minor Hetero Minor

Gene rs # OR(CI95%)1 　 OR(CI95%)2

MTHFR rs1801131 0.97(0.75-1.25) 0.80(0.43-1.47) 0.94(0.71-1.25) 0.88(0.46-1.71)RIZ1 or PRDM2 rs2235515 1.00(0.77-1.31) 0.893(0.64-1.25) 0.96(0.72-1.28) 0.83(0.57-1.21)HSD11B1 rs4393158 0.93(0.72-1.19) 0.94(0.65-1.37) 0.94(0.72-1.24) 0.97(0.64-1.46)HSD11B1 rs17317033 2.18(0.84-5.68) 0(0.0) 2.44(0.83-7.14)HSD11B1 rs2235543 0.92(0.71-1.18) 0.79(0.56-1.13) 0.91(0.69-1.20) 0.78(0.53-1.14)HSD11B1 rs11807619 0.87(0.67-1.13) 0.78(0.41-1.50) 0.94(0.71-1.25) 0.73(0.35-1.54)HSD11B1 rs932335 0.85(0.66-1.11) 0.66(0.31-1.39) 0.91(0.68-1.21) 0.56(0.24-1.32)2p(19150424) rs4666451 0.88(0.55-1.41) 0.87(0.51-1.47)CYP1B1 rs1800440 1.93(0.42-8.84) 1.21(0.25-5.90)CYP1B1 rs1056836 1.20(0.90-1.61) 2.81(0.64-12.43) 1.05(0.77-1.43) 2.38(0.53-10.7)ITGA6 rs17664 1.06(0.80-1.40) 1.00(0.48-2.11) 1.11(0.82-1.51) 1.38(0.58-3.26)ITGAv rs11902171 0.75(0.54-1.05) 1.48(0.31-6.99) 0.72(0.50-1.04) 2.61(0.31-21.8)BARD1 rs6759222 1.03(0.74-1.45) 1.15(0.31-4.27) 0.98(0.68-1.42) 0.72(0.18-2.95)BARD1 rs4673896 1.03(0.80-1.33) 0.87(0.61-1.24) 0.99(0.75-1.30) 0.81(0.55-1.19)BARD1 rs6717301 1.05(0.80-1.38) 0.87(0.63-1.22) 1.10(0.82-1.48) 1.03(0.71-1.47)BARD1 rs2229571 1.22(0.95-1.57) 0.81(0.55-1.18) 1.17(0.89-1.53) 0.80(0.53-1.20)BARD1 rs3768704 1.06(0.81-1.38) 0.84(0.60-1.17) 1.11(0.83-1.48) 0.96(0.66-1.37)BARD1 rs7591615 0.90(0.60-1.36) 1.89(0.22-16.21) 0.81(0.52-1.27) 0.87(0.09-8.57)BARD1 rs6435862 1.16(0.89-1.51) 1.40(0.63-3.12) 1.12(0.84-1.49) 1.02(0.44-2.35)2q35 rs13387042 0.98(0.72-1.33) 1.05(0.33-3.31) 1.11(0.79-1.56) 1.48(0.40-5.47)FGFR2 rs12505080 1.29(0.99-1.69) 1.09(0.78-1.52) 1.35(1.01-1.82) 1.18(0.82-1.69)FGFR2 rs7696175 0.95(0.72-1.25) 1.40(0.56-3.49) 1.05(0.78-1.42) 1.79(0.60-5.35)KIT rs2237038 0.90(0.69-1.16) 0.82(0.58-1.17) 0.88(0.66-1.18) 0.79(0.53-1.16)KIT rs981959 0.90(0.69-1.17) 0.80(0.56-1.14) 0.88(0.66-1.17) 0.75(0.51-1.12)KIT rs2237034 0.89(0.69-1.14) 0.82(0.49-1.37) 0.90(0.68-1.18) 0.95(0.54-1.70)KIT rs2237032 0.89(0.70-1.14) 0.81(0.52-1.26) 0.87(0.66-1.13) 0.85(0.51-1.39)KIT rs2237023 1.03(0.80-1.32) 1.29(0.87-1.90) 1.05(0.79-1.38) 1.02(0.67-1.56)KIT rs6810872 1.01(0.79-1.30) 1.26(0.85-1.85) 1.03(0.78-1.36) 0.99(0.65-1.51)KIT rs3134884 1.14(0.89-1.46) 1.16(0.65-2.10) 1.16(0.89-1.52) 0.83(0.45-1.55)KIT rs3111800 1.01(0.76-1.34) 1.21(0.86-1.70) 0.97(0.71-1.33) 1.07(0.73-1.55)KIT rs2237018 1.07(0.84-1.37) 0.95(0.60-1.50) 1.00(0.76-1.30) 0.94(0.56-1.56)KIT rs6843170 1.10(0.86-1.40) 0.96(0.60-1.53) 1.03(0.79-1.35) 0.93(0.55-1.57)KDR rs17709898 1.27(1.00-1.63) 1.14(0.70-1.85) 1.21(0.93-1.59) 1.13(0.67-1.91)KDR rs12505758 0.97(0.76-1.25) 0.55(0.32-0.95) 0.81(0.62-1.06) 0.50(0.28-0.88)KDR rs2168945 1.07(0.84-1.38) 0.93(0.65-1.34) 1.10(0.84-1.44) 1.19(0.78-1.80)KDR rs13136007 1.21(0.93-1.57) 1.18(0.84-1.65) 1.26(0.95-1.68) 1.18(0.81-1.71)KDR rs11732292 1.07(0.83-1.37) 0.92(0.64-1.33) 1.11(0.85-1.46) 1.15(0.76-1.74)KDR rs1870377 1.25(0.97-1.62) 1.16(0.83-1.63) 1.30(0.97-1.72) 1.19(0.82-1.72)KDR rs7673274 1.00(0.78-1.28) 0.66(0.40-1.08) 0.83(0.63-1.09) 0.57(0.34-0.97)KDR rs11133360 1.16(0.90-1.50) 1.14(0.80-1.62) 1.09(0.83-1.44) 1.16(0.79-1.71)STE or SULT1E1 rs3775775 1.15(0.80-1.66) 1.96(0.43-8.99) 1.04(0.70-1.55) 1.25(0.25-6.22)STE or SULT1E1 rs1881668 1.34(1.04-1.72) 1.40(0.98-2.02) 1.21(0.92-1.60) 1.28(0.86-1.91)ADH1B rs1042026 0.86(0.67-1.11) 1.06(0.53-2.14) 1.00(0.76-1.31) 1.25(0.57-2.73)5p12 rs4415084 0.95(0.73-1.25) 0.70(0.51-0.97) 1.02(0.76-1.37) 0.80(0.56-1.15)MRPS30 rs10941679 1.12(0.85-1.47) 1.27(0.91-1.76) 1.04(0.77-1.41) 1.12(0.78-1.60)5p14 rs7703618 0.84(0.66-1.08) 0.99(0.67-1.46) 0.87(0.67-1.14) 0.94(0.61-1.45)5p15 rs10035564 1.02(0.78-1.33) 0.97(0.69-1.36) 1.06(0.79-1.41) 0.95(0.66-1.37)5p(45321475bp) rs981782 0.98(0.76-1.27) 1.10(0.77-1.56) 1.07(0.81-1.41) 1.10(0.76-1.61)5q(52454339bp) rs30099 0.85(0.66-1.10) 1.11(0.77-1.59) 0.82(0.61-1.09) 1.10(0.74-1.64)MAP3K1 rs889312 0.94(0.71-1.23) 0.87(0.62-1.22) 0.88(0.65-1.19) 0.72(0.50-1.03)DHFR rs1677666 1.24(0.67-2.29) 1.25(0.66-2.37)APC rs11954856 0.81(0.63-1.05) 0.88(0.46-1.70) 0.80(0.60-1.06) 1.07(0.49-2.33)APC rs11241183 0.91(0.71-1.16) 0.89(0.58-1.36) 0.95(0.73-1.24) 0.89(0.56-1.40)OR(95%CI)1: Univariate logistic regression modelOR(95%CI)2: Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

Table 6-1. Association of 384 SNPs with Overall breast cancer risk

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Table 6-2 . Association of 384 SNPs with Overall breast cancer risk　　 Overall (additive model)

Hetero Minor Hetero MinorGene rs # OR(CI95%)1 　 OR(CI95%)2

APC rs2439591 0.82(0.63-1.05) 0.92(0.49-1.74) 0.80(0.60-1.05) 1.09(0.52-2.27)APC rs2431512 0.89(0.70-1.14) 0.88(0.58-1.33) 0.96(0.73-1.26) 0.89(0.57-1.39)APC rs2431238 1.05(0.76-1.44) 0.89(0.34-2.35) 1.09(0.77-1.55) 1.42(0.39-5.14)APC rs454886 0.96(0.75-1.22) 1.09(0.73-1.65) 1.02(0.78-1.33) 1.27(0.81-1.99)APC rs501250 0.97(0.70-1.35) 1.07(0.38-2.99) 0.97(0.68-1.38) 2.04(0.45-9.29)APC rs2229992 0.93(0.73-1.20) 0.89(0.57-1.40) 0.96(0.73-1.25) 0.91(0.56-1.48)APC rs41116 0.91(0.71-1.16) 0.90(0.57-1.44) 0.93(0.71-1.21) 0.93(0.56-1.55)APC rs448475 0.90(0.70-1.14) 0.94(0.59-1.49) 0.91(0.70-1.20) 0.98(0.59-1.63)CDKN1A rs3176336 1.26(0.98-1.61) 0.89(0.57-1.39) 1.34(1.02-1.75) 1.10(0.68-1.79)CDKN1A rs1801270 0.80(0.60-1.05) 0.81(0.58-1.13) 0.72(0.53-0.97) 0.71(0.49-1.02)CCND3 rs2479717 0.93(0.67-1.30) 0.95(0.67-1.37)LSP1 rs381798 1.00(0.77-1.29) 0.89(0.63-1.26) 1.00(0.75-1.32) 0.97(0.66-1.41)ECHDC1 rs2180341 1.00(0.78-1.27) 1.31(0.84-2.06) 1.06(0.81-1.38) 1.35(0.82-2.23)ECHDC1 rs6569479 0.99(0.78-1.27) 1.31(0.83-2.05) 1.05(0.80-1.38) 1.35(0.82-2.23)ECHDC1 rs6569480 1.00(0.79-1.28) 1.31(0.83-2.06) 1.06(0.81-1.39) 1.35(0.82-2.23)ECHDC1 rs7776136 1.00(0.78-1.27) 1.31(0.84-2.07) 1.05(0.80-1.37) 1.36(0.83-2.25)ESR1 rs851984 1.07(0.80-1.43) 0.50(0.22-1.15) 1.01(0.74-1.39) 0.41(0.17-0.97)ESR1 rs851982 1.04(0.78-1.38) 0.53(0.23-1.21) 0.97(0.71-1.33) 0.44(0.19-1.02)ESR1 rs2881766 1.33(1.03-1.72) 1.17(0.83-1.66) 1.44(1.09-1.91) 1.24(0.85-1.81)ESR1 rs2077647 1.23(0.95-1.58) 1.30(0.90-1.85) 1.37(1.04-1.80) 1.46(0.98-2.17)ESR1 rs9322331 1.29(0.72-2.33) 1.16(0.63-2.13)ESR1 rs712221 1.10(0.84-1.43) 1.23(0.88-1.72) 1.17(0.88-1.56) 1.25(0.87-1.81)ESR1 rs1801132 0.86(0.65-1.14) 0.82(0.59-1.14) 0.82(0.60-1.12) 0.76(0.53-1.09)ESR1 rs3020314 1.10(0.85-1.42) 1.02(0.52-2.01) 1.19(0.90-1.58) 1.04(0.49-2.22)ESR1 rs3020377 1.11(0.86-1.43) 0.94(0.49-1.83) 1.21(0.91-1.60) 0.95(0.46-1.97)ESR1 rs3020390 0.92(0.72-1.18) 0.97(0.66-1.43) 0.98(0.75-1.29) 0.92(0.60-1.40)ESR1 rs3020317 0.85(0.65-1.11) 1.02(0.73-1.43) 0.87(0.65-1.17) 1.00(0.69-1.43)ESR1 rs3020394 0.94(0.73-1.20) 0.93(0.64-1.35) 1.01(0.77-1.32) 0.88(0.59-1.31)ESR1 rs3020396 0.92(0.72-1.18) 0.89(0.62-1.29) 0.98(0.75-1.30) 0.83(0.56-1.23)ESR1 rs3020401 0.93(0.72-1.19) 0.90(0.62-1.30) 0.99(0.75-1.30) 0.84(0.56-1.24)ESR1 rs1884051 0.92(0.70-1.22) 0.88(0.64-1.23) 0.93(0.69-1.25) 0.85(0.60-1.21)ESR1 rs1884054 0.95(0.75-1.21) 1.05(0.67-1.65) 1.06(0.81-1.39) 1.00(0.62-1.63)ESR1 rs3020405 0.96(0.75-1.23) 1.01(0.65-1.57) 1.08(0.83-1.42) 0.96(0.60-1.53)ESR1 rs726282 0.88(0.68-1.14) 0.89(0.63-1.26) 0.91(0.69-1.21) 0.85(0.59-1.24)ESR1 rs3020407 0.95(0.74-1.21) 1.14(0.75-1.74) 1.07(0.82-1.40) 1.11(0.70-1.74)ESR1 rs6905370 0.96(0.73-1.25) 0.98(0.70-1.38) 0.85(0.64-1.15) 0.96(0.66-1.39)ESR1 rs926778 1.46(1.13-1.88) 1.12(0.79-1.58) 1.59(1.20-2.10) 1.28(0.88-1.88)ESR1 rs3020366 1.21(0.93-1.58) 0.79(0.56-1.10) 1.07(0.80-1.43) 0.69(0.48-1.00)ESR1 rs2273206 1.39(1.08-1.77) 1.09(0.74-1.60) 1.43(1.09-1.88) 1.13(0.74-1.72)ESR1 rs750686 1.07(0.82-1.41) 0.80(0.57-1.11) 0.92(0.68-1.24) 0.68(0.47-0.98)ESR1 rs2228480 0.81(0.64-1.04) 0.53(0.29-1.00) 0.83(0.64-1.09) 0.64(0.31-1.33)ESR1 rs3798577 0.68(0.53-0.88) 0.78(0.55-1.12) 0.68(0.51-0.90) 0.84(0.56-1.25)ESR1 rs910416 0.88(0.68-1.13) 0.70(0.49-1.01) 0.89(0.67-1.18) 0.75(0.51-1.12)IGFBP3 rs2854744 1.29(1.00-1.67) 0.59(0.37-0.94) 1.25(0.94-1.66) 0.50(0.30-0.83)EGFR rs11770506 0.94(0.74-1.21) 0.71(0.47-1.05) 0.93(0.71-1.21) 0.67(0.43-1.04)EGFR rs4947974 0.97(0.76-1.24) 0.88(0.59-1.31) 0.91(0.70-1.19) 1.00(0.64-1.57)EGFR rs2110290 1.03(0.81-1.32) 0.87(0.57-1.31) 0.98(0.75-1.28) 1.03(0.64-1.64)EGFR rs12667668 1.19(0.93-1.52) 0.87(0.59-1.29) 1.16(0.88-1.52) 0.92(0.59-1.43)EGFR rs12718945 1.17(0.92-1.50) 0.92(0.62-1.37) 1.13(0.86-1.48) 0.99(0.63-1.54)EGFR rs6593207 1.35(1.06-1.73) 0.88(0.57-1.36) 1.31(1.00-1.72) 0.90(0.56-1.47)EGFR rs2072454 1.24(0.96-1.59) 0.91(0.63-1.32) 1.20(0.91-1.58) 0.86(0.57-1.29)EGFR rs11536635 1.15(0.89-1.48) 1.02(0.72-1.45) 1.21(0.91-1.61) 0.96(0.66-1.41)EGFR rs11977388 1.29(1.01-1.65) 0.80(0.54-1.20) 1.33(1.01-1.74) 0.75(0.48-1.15)EGFR rs10228436 1.31(1.02-1.69) 0.96(0.68-1.36) 1.38(1.04-1.82) 0.92(0.63-1.34)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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Table 6-3. Association of 384 SNPs with Overall breast cancer risk　　 Overall (additive model)


ABCB1 rs1045642 1.11(0.87-1.43) 1.05(0.72-1.53) 1.07(0.81-1.40) 0.98(0.65-1.47)ABCB1 rs7787082 1.09(0.84-1.43) 1.13(0.80-1.58) 1.04(0.78-1.40) 1.07(0.74-1.55)ABCB1 rs2091766 0.88(0.68-1.13) 0.71(0.50-1.01) 0.97(0.74-1.28) 0.81(0.55-1.20)ABCB1 rs1128503 0.93(0.72-1.21) 0.74(0.53-1.04) 1.00(0.75-1.32) 0.82(0.56-1.19)ABCB1 rs1922241 0.89(0.69-1.14) 0.70(0.49-1.01) 0.99(0.75-1.30) 0.80(0.54-1.19)ABCB1 rs868755 0.91(0.71-1.18) 1.13(0.78-1.64) 0.91(0.69-1.19) 1.09(0.73-1.64)ABCB1 rs2520464 0.93(0.72-1.21) 0.71(0.50-1.00) 0.99(0.74-1.31) 0.76(0.52-1.11)ABCB1 rs1202184 1.03(0.80-1.33) 0.68(0.47-0.98) 1.05(0.80-1.39) 0.72(0.48-1.07)ABCB1 rs12535512 0.98(0.75-1.28) 0.99(0.70-1.40) 1.03(0.77-1.38) 1.00(0.69-1.46)ABCB1 rs12720464 1.23(0.96-1.56) 1.49(0.86-2.57) 1.09(0.84-1.43) 1.46(0.82-2.59)ABCB1 rs1978095 1.26(0.99-1.61) 1.45(0.85-2.47) 1.13(0.86-1.47) 1.41(0.80-2.48)CDK6 rs3757823 0.91(0.68-1.22) 0.61(0.44-0.85) 0.85(0.61-1.18) 0.59(0.41-0.85)Q129R rs662 0.86(0.67-1.11) 0.64(0.43-0.94) 0.86(0.66-1.14) 0.63(0.42-0.96)L55M rs854560 0.90(0.63-1.28) 1.89(0.22-16.2) 0.92(0.62-1.35) 1.45(0.16-13.1)FGFR2 rs17157903 0.99(0.77-1.27) 1.21(0.73-2.03) 1.01(0.77-1.33) 1.65(0.92-2.95)MET rs2237710 1.08(0.84-1.40) 0.88(0.62-1.25) 1.12(0.85-1.48) 0.93(0.63-1.35)MET rs2299437 1.04(0.82-1.34) 0.91(0.62-1.34) 1.07(0.81-1.40) 0.95(0.63-1.45)MET rs10248537 1.04(0.82-1.34) 0.93(0.63-1.36) 1.06(0.81-1.40) 0.97(0.64-1.47)MET rs38855 1.21(0.94-1.57) 1.22(0.87-1.71) 1.32(1.00-1.75) 1.19(0.82-1.71)MET rs38858 1.23(0.95-1.59) 1.23(0.88-1.73) 1.33(1.01-1.77) 1.20(0.83-1.74)MET rs13223756 1.13(0.88-1.44) 0.79(0.51-1.22) 1.19(0.90-1.56) 0.71(0.44-1.14)MET rs2299440 1.12(0.88-1.44) 0.78(0.51-1.21) 1.19(0.91-1.56) 0.71(0.44-1.13)MET rs183642 1.32(0.99-1.75) 0.91(0.66-1.25) 1.32(0.97-1.80) 0.83(0.59-1.18)MET rs41736 1.34(1.01-1.77) 0.92(0.67-1.26) 1.35(0.99-1.83) 0.84(0.59-1.19)MET rs41739 1.36(1.03-1.81) 0.92(0.67-1.26) 1.37(1.01-1.87) 0.85(0.60-1.21)TBXAS1 rs6971207 1.17(0.92-1.50) 1.19(0.80-1.77) 1.19(0.91-1.56) 1.06(0.70-1.62)FGFR1 rs2304000 1.09(0.85-1.40) 1.13(0.77-1.66) 1.19(0.90-1.56) 1.18(0.78-1.79)FGFR1 rs4647907 1.08(0.85-1.39) 1.19(0.81-1.75) 1.17(0.89-1.54) 1.25(0.82-1.89)FGFR1 rs2956724 0.92(0.72-1.17) 0.99(0.63-1.56) 0.86(0.66-1.12) 0.88(0.54-1.43)FGFR1 rs2978073 0.88(0.69-1.13) 1.03(0.65-1.62) 0.83(0.64-1.09) 0.91(0.56-1.48)FGFR1 rs6983315 0.84(0.65-1.08) 1.04(0.71-1.51) 0.82(0.63-1.08) 1.08(0.72-1.63)FGFR1 rs6987534 0.87(0.68-1.11) 1.01(0.69-1.47) 0.87(0.66-1.14) 1.07(0.71-1.63)NBS1 rs9995 1.09(0.84-1.41) 0.78(0.56-1.09) 1.08(0.81-1.43) 0.71(0.49-1.02)NBS1 or NBN rs1805787 0.57(0.20-1.61) 0.48(0.16-1.41)8q24 rs13281615 0.87(0.67-1.13) 1.08(0.76-1.52) 0.98(0.74-1.31) 1.03(0.71-1.50)MYC rs3891248 0.96(0.74-1.25) 1.09(0.77-1.54) 1.06(0.79-1.41) 1.13(0.77-1.65)CDKN2A rs3731239 0.83(0.63-1.08) 0.54(0.26-1.13) 0.81(0.60-1.09) 0.43(0.19-0.93)MCS5A6 rs2182317 0.98(0.76-1.26) 0.80(0.43-1.51) 1.00(0.75-1.33) 0.64(0.33-1.23)EHMT1 rs4634736 1.15(0.23-5.71) 1.03(0.19-5.41)FLJ45983 rs1149901 0.82(0.57-1.17) 0.87(0.22-3.38) 0.78(0.54-1.15) 0.69(0.17-2.78)GATA3 rs570613 0.65(0.50-0.83) 0.66(0.45-0.95) 0.72(0.54-0.94) 0.68(0.46-1.02)GATA3 rs422628 0.82(0.57-1.17) 2.24(0.27-18.7) 0.82(0.56-1.20) 2.35(0.28-19.7)FGFR2 rs11200014 1.14(0.89-1.45) 1.04(0.67-1.62) 1.21(0.92-1.58) 1.05(0.65-1.69)FGFR2 rs2981579 1.11(0.85-1.44) 1.31(0.93-1.85) 1.13(0.85-1.50) 1.45(0.99-2.11)FGFR2 rs1078806 1.15(0.90-1.46) 0.99(0.63-1.55) 1.23(0.94-1.60) 1.01(0.62-1.64)FGFR2 rs1219648 1.16(0.90-1.50) 1.25(0.87-1.79) 1.13(0.85-1.49) 1.30(0.87-1.93)FGFR2 rs2420946 1.26(0.98-1.62) 1.27(0.89-1.81) 1.21(0.92-1.60) 1.30(0.88-1.91)FGFR2 rs2981582 1.35(1.05-1.73) 1.04(0.70-1.55) 1.33(1.02-1.75) 1.12(0.72-1.73)FGFR2 rs10510126 1.13(0.76-1.69) 1.27(0.82-1.98)LSP1 rs661348 1.20(0.93-1.55) 1.10(0.77-1.55) 1.16(0.87-1.53) 0.91(0.62-1.32)LSP1 rs3817198 0.97(0.74-1.27) 1.06(0.49-2.29) 0.97(0.73-1.30) 0.76(0.34-1.72)H19 rs2107425 0.84(0.64-1.11) 0.74(0.53-1.03) 0.83(0.61-1.12) 0.74(0.51-1.07)CCND1 rs3212891 0.88(0.67-1.16) 1.27(0.46-3.47) 0.87(0.64-1.17) 1.04(0.37-2.95)CCND1 rs678653 0.92(0.70-1.22) 1.28(0.47-3.51) 0.93(0.69-1.26) 1.06(0.38-3.03)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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NUMA1 rs3750913 0.85(0.59-1.22) 0.56(0.09-3.38) 0.85(0.58-1.26) 0.51(0.08-3.11)PGR rs500760 0.94(0.73-1.21) 1.33(0.60-2.95) 0.94(0.72-1.24) 1.29(0.57-2.93)PGR rs511298 0.96(0.74-1.24) 1.31(0.56-3.08) 0.97(0.74-1.29) 1.18(0.49-2.83)PGR rs1042839 3.45(0.44-27.32) 3.45(0.44-27.32) 1.02(1.00-1.04) 3.42(0.43-27.3)PGR rs1042838 3.85(0.49-30.17) 3.72(0.47-29.4)PGR rs660149 0.99(0.50-1.95) 0.93(0.45-1.91)PGR rs2020876 0.86(0.37-1.99) 0.99(0.38-2.61)PGR rs7116336 1.04(0.81-1.35) 1.13(0.56-2.28) 1.04(0.78-1.37) 1.09(0.53-2.24)PGR rs11571171 0.98(0.75-1.27) 2.12(0.72-6.20) 0.98(0.74-1.31) 1.97(0.66-5.86)PGR rs566351 1.12(0.87-1.45) 0.97(0.44-2.13) 1.13(0.85-1.49) 1.04(0.45-2.42)PGR rs506487 0.76(0.14-4.19) 1.02(1.00-1.04) 0.83(0.15-4.68)PGR rs518162 1.29(0.65-2.56) 1.27(0.61-2.62)MMP8 rs1892886 1.18(0.85-1.64) 0.62(0.20-1.92) 1.08(0.75-1.55) 0.60(0.19-1.87)CDKN1B rs34330 1.09(0.84-1.42) 1.25(0.90-1.74) 1.07(0.80-1.43) 1.18(0.82-1.68)IGF1 rs2946834 0.93(0.71-1.22) 0.81(0.59-1.12) 0.85(0.63-1.15) 0.72(0.50-1.03)IGF1 rs5742714 0.97(0.74-1.26) 1.09(0.58-2.03) 0.89(0.67-1.19) 1.01(0.52-1.95)IGF1 rs6214 0.88(0.66-1.16) 0.85(0.61-1.17) 0.90(0.66-1.23) 0.92(0.65-1.31)IGF1 rs1520220 1.04(0.80-1.36) 0.82(0.59-1.14) 0.95(0.71-1.28) 0.73(0.51-1.05)IGF1 rs10745940 1.04(0.80-1.35) 0.82(0.59-1.15) 0.95(0.71-1.27) 0.74(0.51-1.06)IGF1 rs5742694 0.99(0.76-1.29) 1.04(0.55-1.95) 0.92(0.69-1.23) 0.94(0.48-1.84)IGF1 rs978458 1.05(0.81-1.37) 0.82(0.59-1.14) 0.95(0.71-1.28) 0.74(0.51-1.05)IGF1 rs5742667 1.05(0.80-1.37) 0.81(0.59-1.13) 0.97(0.73-1.30) 0.73(0.51-1.04)IGF1 rs2373721 0.95(0.73-1.24) 1.20(0.63-2.27) 0.87(0.65-1.15) 1.12(0.57-2.19)IGF1 rs7136446 0.96(0.74-1.25) 1.27(0.67-2.39) 0.86(0.65-1.15) 1.14(0.58-2.24)IGF1 rs9989002 0.83(0.63-1.08) 1.36(0.67-2.78) 0.76(0.57-1.01) 1.24(0.58-2.66)IGF1 rs5742632 1.03(0.79-1.34) 0.70(0.50-0.98) 0.96(0.72-1.28) 0.63(0.44-0.91)IGF1 rs2195240 1.03(0.79-1.34) 0.72(0.51-1.00) 0.95(0.72-1.27) 0.65(0.45-0.94)IGF1 rs5742629 1.04(0.80-1.35) 0.72(0.52-1.01) 0.97(0.73-1.29) 0.65(0.45-0.94)IGF1 rs7956547 0.88(0.68-1.16) 1.04(0.50-2.17) 0.80(0.59-1.07) 0.96(0.44-2.11)IGF1 rs4764698 0.93(0.73-1.19) 0.74(0.48-1.15) 0.94(0.72-1.23) 0.69(0.42-1.11)IGF1 rs10778176 1.07(0.83-1.40) 0.70(0.50-0.97) 1.00(0.75-1.34) 0.64(0.44-0.91)IGF1 rs2162679 0.94(0.73-1.20) 0.86(0.59-1.26) 0.89(0.68-1.17) 0.81(0.54-1.22)IGF1 rs35765 1.48(0.96-2.28) 0.13(0.01-1.26) 1.40(0.88-2.21) 0.15(0.02-1.46)IGF1 rs7965399 0.95(0.75-1.21) 0.97(0.61-1.53) 0.91(0.70-1.18) 0.91(0.55-1.50)IGF1 rs855211 0.98(0.77-1.26) 0.99(0.66-1.50) 0.95(0.73-1.24) 0.91(0.58-1.42)BRCA2 rs144848 0.91(0.71-1.16) 1.46(0.85-2.51) 0.88(0.67-1.14) 1.85(0.99-3.45)BRCA2 rs4942485 0.84(0.49-1.44) 0.84(0.47-1.49)IRS2 rs9515118 1.16(0.91-1.49) 0.83(0.54-1.30) 1.23(0.94-1.62) 0.86(0.54-1.37)IRS2 rs4773082 0.97(0.76-1.24) 0.85(0.52-1.38) 0.93(0.71-1.21) 0.89(0.51-1.55)IRS2 rs2289046 1.04(0.79-1.37) 1.11(0.79-1.55) 1.04(0.77-1.40) 1.07(0.75-1.55)IRS2 rs754204 0.87(0.68-1.11) 1.13(0.72-1.77) 0.85(0.65-1.11) 1.17(0.71-1.94)IRS2 rs7987237 1.08(0.84-1.38) 0.84(0.51-1.38) 1.16(0.88-1.52) 0.82(0.49-1.38)IRS2 rs12584136 0.99(0.65-1.51) 1.01(0.64-1.60)IRS2 rs9559648 0.89(0.70-1.14) 1.11(0.60-2.07) 0.86(0.66-1.13) 1.08(0.53-2.17)IRS2 rs9559654 1.00(0.78-1.29) 1.30(0.65-2.59) 0.97(0.73-1.28) 1.36(0.64-2.89)IRS2 rs7997595 1.03(0.80-1.32) 0.74(0.47-1.17) 1.02(0.78-1.34) 0.80(0.49-1.30)IRS2 rs7981705 0.84(0.51-1.39) 1.02(0.59-1.76)IRS2 rs4773092 1.13(0.86-1.48) 0.95(0.68-1.31) 1.11(0.82-1.50) 0.94(0.66-1.34)ESR2 rs1255998 1.17(0.90-1.53) 1.17(0.84-1.63) 1.19(0.89-1.60) 1.16(0.80-1.67)ESR2 rs8018687 0.99(0.72-1.37) 0.76(0.19-3.06) 1.00(0.70-1.43) 0.61(0.14-2.61)ESR2 rs928554 0.97(0.75-1.25) 0.92(0.64-1.32) 1.00(0.76-1.31) 1.01(0.67-1.52)ESR2 rs1152579 0.98(0.76-1.25) 0.90(0.62-1.29) 1.00(0.76-1.32) 0.99(0.66-1.49)ESR2 rs1256049 1.07(0.84-1.37) 1.30(0.82-2.06) 1.13(0.86-1.47) 1.25(0.76-2.06)ESR2 rs1256030 1.00(0.78-1.29) 0.95(0.66-1.36) 1.00(0.76-1.31) 1.05(0.70-1.56)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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ESR2 rs1271572 1.01(0.78-1.30) 0.93(0.65-1.33) 1.00(0.76-1.32) 1.01(0.67-1.51)XRCC3 rs861539 1.15(0.75-1.77) 1.04(0.64-1.68)XRCC3 rs1799796 0.91(0.71-1.16) 0.78(0.53-1.15) 0.84(0.64-1.10) 0.77(0.50-1.18)XRCC3 rs1799794 0.99(0.75-1.31) 0.90(0.65-1.25) 0.87(0.64-1.19) 0.85(0.59-1.21)AKT1 rs2494744 1.10(0.86-1.42) 1.17(0.81-1.69) 1.05(0.80-1.37) 1.25(0.83-1.89)AKT1 rs2498787 0.98(0.76-1.26) 1.14(0.79-1.65) 0.93(0.71-1.22) 1.25(0.83-1.88)CYP20 rs4646 0.98(0.77-1.25) 0.87(0.58-1.32) 1.02(0.78-1.34) 0.91(0.58-1.43)CYP19 rs10046 0.95(0.73-1.25) 1.03(0.74-1.44) 0.97(0.72-1.31) 1.10(0.76-1.59)CYP21 rs727479 0.90(0.71-1.15) 0.81(0.54-1.21) 0.96(0.73-1.26) 0.87(0.57-1.34)MAP2K1 rs7174378 0.95(0.72-1.25) 0.85(0.61-1.19) 1.00(0.74-1.34) 0.89(0.62-1.29)MAP2K1 rs7181936 1.02(0.79-1.31) 1.13(0.79-1.61) 1.08(0.82-1.42) 1.15(0.78-1.70)MAP2K1 rs28620576 1.03(0.80-1.31) 1.25(0.81-1.93) 1.18(0.90-1.54) 1.19(0.75-1.91)MAP2K1 rs8039880 0.91(0.70-1.18) 0.81(0.57-1.14) 0.95(0.72-1.26) 0.83(0.57-1.21)CYP1A1 rs1048943 1.24(0.97-1.59) 1.58(0.89-2.80) 1.34(1.02-1.76) 1.36(0.73-2.55)IGF1R rs4966007 1.11(0.86-1.43) 1.19(0.84-1.69) 1.29(0.98-1.70) 1.44(0.98-2.11)IGF1R rs8028620 1.10(0.83-1.45) 1.09(0.79-1.50) 1.27(0.94-1.72) 1.32(0.92-1.88)IGF1R rs4966009 1.10(0.85-1.42) 1.21(0.85-1.72) 1.29(0.98-1.71) 1.45(0.98-2.14)IGF1R rs8027457 1.13(0.85-1.49) 1.10(0.80-1.52) 1.31(0.97-1.77) 1.31(0.91-1.86)IGF1R rs4966012 0.92(0.72-1.17) 0.91(0.59-1.41) 0.90(0.69-1.17) 0.88(0.55-1.41)IGF1R rs1574213 0.95(0.74-1.22) 1.71(0.87-3.34) 0.92(0.70-1.21) 1.54(0.75-3.17)IGF1R rs11630479 0.91(0.72-1.17) 0.91(0.59-1.42) 0.94(0.72-1.22) 0.86(0.53-1.39)IGF1R rs4966013 1.02(0.78-1.34) 1.08(0.78-1.50) 1.10(0.81-1.48) 1.04(0.73-1.48)IGF1R rs4966015 0.89(0.69-1.13) 1.08(0.61-1.91) 0.92(0.70-1.20) 1.11(0.60-2.05)IGF1R rs8032477 0.99(0.75-1.30) 0.74(0.53-1.03) 1.03(0.76-1.40) 0.69(0.48-0.99)IGF1R rs11634241 0.87(0.68-1.11) 1.00(0.66-1.49) 0.92(0.70-1.21) 0.90(0.58-1.40)IGF1R rs932071 0.85(0.67-1.10) 0.83(0.48-1.43) 0.90(0.69-1.19) 0.66(0.37-1.19)IGF1R rs875686 0.86(0.67-1.09) 0.81(0.50-1.34) 0.91(0.70-1.19) 0.77(0.44-1.33)IGF1R rs1567811 0.99(0.77-1.28) 0.81(0.56-1.16) 1.03(0.78-1.36) 0.78(0.52-1.15)IGF1R rs11632952 0.87(0.68-1.11) 0.88(0.52-1.49) 0.94(0.72-1.24) 0.65(0.37-1.13)IGF1R rs4966024 0.94(0.71-1.25) 0.90(0.64-1.26) 1.02(0.75-1.39) 0.88(0.61-1.26)IGF1R rs8041224 0.93(0.72-1.21) 0.74(0.52-1.05) 0.97(0.73-1.30) 0.68(0.46-1.00)IGF1R rs7175052 0.95(0.74-1.23) 0.69(0.48-0.97) 1.01(0.77-1.34) 0.62(0.42-0.90)IGF1R rs2137680 1.06(0.80-1.40) 0.84(0.61-1.17) 1.17(0.86-1.59) 0.81(0.57-1.15)IGF1R rs12439557 0.95(0.74-1.22) 0.69(0.45-1.05) 1.07(0.81-1.40) 0.58(0.36-0.92)IGF1R rs4966028 0.95(0.72-1.24) 1.25(0.61-2.58) 0.93(0.69-1.25) 1.49(0.67-3.29)IGF1R rs907806 0.89(0.68-1.17) 1.61(0.70-3.69) 0.88(0.65-1.18) 2.16(0.82-5.67)IGF1R rs8041953 0.91(0.70-1.18) 1.25(0.59-2.67) 0.92(0.68-1.23) 1.61(0.69-3.74)IGF1R rs2670501 0.81(0.62-1.05) 0.85(0.60-1.21) 0.82(0.62-1.09) 0.79(0.54-1.16)IGF1R rs4246340 1.00(0.77-1.31) 1.32(0.94-1.85) 1.01(0.75-1.36) 1.27(0.88-1.83)IGF1R rs2684777 0.84(0.65-1.09) 1.01(0.71-1.44) 0.91(0.69-1.20) 1.07(0.72-1.57)IGF1R rs8030950 1.11(0.87-1.43) 0.89(0.54-1.47) 1.11(0.84-1.45) 0.86(0.50-1.48)IGF1R rs12594847 1.03(0.80-1.33) 1.05(0.73-1.51) 1.04(0.79-1.38) 1.01(0.68-1.49)IGF1R rs2684781 1.01(0.79-1.30) 0.99(0.70-1.41) 1.03(0.78-1.36) 0.94(0.64-1.37)IGF1R rs1521481 1.11(0.86-1.42) 0.79(0.49-1.29) 1.06(0.81-1.39) 0.74(0.44-1.26)IGF1R rs4966035 0.76(0.58-1.01) 0.95(0.69-1.33) 0.69(0.51-0.94) 0.87(0.60-1.25)IGF1R rs4966036 0.87(0.67-1.12) 0.99(0.69-1.42) 0.94(0.71-1.24) 1.11(0.74-1.64)IGF1R rs7165875 0.80(0.61-1.05) 1.00(0.72-1.39) 0.71(0.53-0.96) 0.90(0.63-1.29)IGF1R rs3743259 0.75(0.57-0.99) 1.02(0.73-1.43) 0.68(0.50-0.92) 0.93(0.65-1.35)IGF1R rs3743260 1.13(0.86-1.49) 0.97(0.47-1.97) 1.13(0.84-1.53) 0.95(0.45-2.02)IGF1R rs2684810 1.17(0.91-1.49) 0.96(0.62-1.49) 1.05(0.80-1.37) 0.88(0.55-1.42)IGF1R rs4966039 0.96(0.74-1.23) 0.78(0.40-1.50) 0.88(0.67-1.16) 0.77(0.39-1.53)IGF1R rs2684805 1.15(0.88-1.49) 1.20(0.85-1.68) 1.27(0.95-1.69) 1.27(0.88-1.85)IGF1R rs2684803 1.28(1.00-1.65) 1.11(0.76-1.62) 1.35(1.03-1.78) 1.11(0.74-1.65)IGF1R rs1546713 1.28(1.00-1.64) 1.10(0.75-1.60) 1.35(1.02-1.77) 1.11(0.74-1.65)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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IGF1R rs7166558 1.29(1.01-1.66) 1.14(0.78-1.66) 1.36(1.04-1.79) 1.14(0.76-1.70)IGF1R rs2229765 1.28(1.00-1.64) 1.14(0.78-1.67) 1.35(1.03-1.77) 1.14(0.76-1.71)IGF1R rs11635251 1.00(0.78-1.28) 0.66(0.44-0.99) 0.96(0.73-1.25) 0.59(0.38-0.91)IGF1R rs8038056 1.22(0.95-1.56) 0.69(0.46-1.03) 1.28(0.98-1.69) 0.73(0.47-1.15)IGF1R rs12916884 1.07(0.83-1.37) 0.54(0.37-0.80) 1.01(0.77-1.32) 0.54(0.36-0.82)IGF1R rs7173377 1.25(0.97-1.61) 0.94(0.64-1.37) 1.26(0.96-1.65) 0.95(0.62-1.45)IGF1R rs7166565 1.27(0.99-1.63) 0.97(0.67-1.41) 1.28(0.97-1.68) 1.01(0.67-1.52)IGF1R rs939626 1.03(0.81-1.33) 0.59(0.37-0.94) 1.02(0.78-1.34) 0.63(0.37-1.05)IGF1R rs12437963 1.12(0.87-1.44) 1.20(0.83-1.71) 1.15(0.87-1.52) 1.21(0.82-1.78)IGF1R rs2684788 0.98(0.75-1.29) 1.03(0.74-1.44) 0.99(0.74-1.34) 1.08(0.75-1.54)IGF1R rs1815009 1.12(0.85-1.46) 1.05(0.76-1.45) 1.16(0.86-1.56) 1.08(0.76-1.53)A2BP1 rs7203563 0.86(0.67-1.11) 0.86(0.45-1.63) 0.86(0.65-1.13) 1.02(0.49-2.15)TNRC9/LOC643714 rs8051542 1.21(0.94-1.55) 1.46(0.79-2.68) 1.17(0.89-1.53) 1.28(0.67-2.46)TNRC9/LOC643714 rs12443621 1.03(0.80-1.32) 1.09(0.75-1.59) 1.02(0.77-1.34) 1.09(0.72-1.63)TNRC9 or TOX3 rs3803662 0.73(0.57-0.94) 0.67(0.47-0.96) 0.72(0.55-0.95) 0.63(0.43-0.94)ATP1B2 rs1641512 1.01(0.79-1.31) 0.83(0.59-1.18) 1.04(0.79-1.37) 0.90(0.62-1.33)TP53 rs9894946 1.10(0.69-1.74) 1.00(0.61-1.65)TP53 rs1614984 0.88(0.69-1.13) 0.76(0.52-1.11) 0.89(0.68-1.17) 0.87(0.56-1.34)TP53 rs1042522 0.82(0.64-1.06) 0.75(0.53-1.08) 0.79(0.60-1.05) 0.83(0.55-1.24)WDR79 rs2287499 0.80(0.63-1.02) 0.83(0.49-1.41) 0.78(0.59-1.01) 0.85(0.46-1.56)WDR79 rs17885803 0.86(0.63-1.18) 1.87(0.41-8.58) 0.83(0.59-1.18) 1.82(0.39-8.40)WDR79 rs2287498 0.81(0.63-1.03) 0.83(0.49-1.42) 0.78(0.60-1.02) 0.85(0.46-1.57)HER2 rs1565923 1.15(0.89-1.48) 1.32(0.92-1.89) 1.10(0.83-1.46) 1.22(0.83-1.81)ERBB rs1810132 1.15(0.89-1.49) 1.31(0.92-1.88) 1.11(0.83-1.47) 1.22(0.83-1.80)HER2 rs3809717 1.01(0.79-1.29) 1.16(0.73-1.83) 0.99(0.76-1.29) 1.02(0.63-1.66)ITGB3 rs3809865 0.99(0.77-1.27) 1.13(0.63-2.02) 1.04(0.79-1.37) 1.15(0.61-2.16)ITGA3 rs1062484 0.53(0.17-1.69) 0.55(0.15-1.99)AXIN2 rs7210356 1.09(0.82-1.44) 0.71(0.35-1.45) 0.99(0.73-1.35) 0.68(0.31-1.49)AXIN2 rs4791171 0.86(0.67-1.10) 0.73(0.51-1.06) 0.78(0.60-1.03) 0.63(0.42-0.94)AXIN2 rs11079571 1.20(0.94-1.54) 1.30(0.84-2.02) 1.15(0.88-1.51) 1.50(0.90-2.49)AXIN2 rs3923087 0.86(0.67-1.10) 0.87(0.59-1.27) 0.81(0.62-1.06) 0.78(0.52-1.19)AXIN2 rs3923086 0.83(0.64-1.08) 0.72(0.33-1.56) 0.84(0.63-1.12) 0.69(0.30-1.60)GPX4 rs4807542 1.05(0.81-1.35) 0.62(0.35-1.12) 1.10(0.83-1.46) 0.69(0.36-1.34)MAP2K2 rs350916 1.18(0.92-1.51) 0.96(0.65-1.40) 1.21(0.92-1.59) 0.88(0.59-1.32)MAP2K2 rs350913 1.28(1.00-1.65) 0.91(0.63-1.32) 1.34(1.02-1.77) 0.84(0.57-1.25)MAP2K2 rs7258366 1.45(1.13-1.85) 1.09(0.72-1.65) 1.52(1.16-1.99) 1.00(0.64-1.55)MAP2K2 rs350894 1.22(0.95-1.58) 1.17(0.82-1.68) 1.35(1.02-1.79) 1.13(0.77-1.66)MAP2K2 rs12459484 1.50(1.17-1.94) 1.26(0.89-1.81) 1.57(1.19-2.07) 1.18(0.80-1.74)ICAM5 rs1056538 1.02(0.80-1.30) 1.17(0.78-1.77) 0.97(0.74-1.27) 1.03(0.66-1.60)CCNE1 rs997669 1.17(0.85-1.62) 1.28(0.41-3.95) 1.26(0.88-1.80) 1.64(0.44-6.02)XRCC1 rs25487 1.18(0.92-1.51) 1.57(0.90-2.74) 1.21(0.93-1.58) 1.38(0.75-2.53)PTGIS rs6095541 0.88(0.64-1.22) 3.02(0.38-24.21) 0.88(0.62-1.26) 2.54(0.31-20.5)PTGIS rs6095543 0.98(0.75-1.28) 1.07(0.51-2.23) 0.95(0.71-1.27) 1.05(0.46-2.39)PTGIS rs693649 1.06(0.82-1.37) 0.90(0.63-1.28) 1.05(0.79-1.38) 1.06(0.71-1.56)AURKA rs8173 1.02(0.79-1.30) 1.55(1.03-2.33) 1.02(0.78-1.34) 1.48(0.95-2.29)AURKA rs10485805 0.92(0.73-1.18) 1.52(0.85-2.74) 0.93(0.71-1.22) 1.38(0.73-2.62)AURKA rs6024840 1.13(0.88-1.45) 0.84(0.56-1.25) 1.18(0.90-1.55) 0.78(0.50-1.21)AURKA rs911160 1.11(0.87-1.42) 0.87(0.58-1.30) 1.18(0.90-1.55) 0.78(0.51-1.20)AURKA rs2298016 1.04(0.81-1.34) 0.87(0.60-1.28) 1.08(0.82-1.41) 0.78(0.52-1.19)AURKA rs2273535 1.07(0.83-1.37) 0.88(0.60-1.28) 1.09(0.83-1.44) 0.78(0.52-1.18)COMT rs4680 0.74(0.58-0.95) 1.08(0.67-1.75) 0.74(0.57-0.97) 1.06(0.62-1.80)CHEK2 rs9608698 0.84(0.66-1.07) 1.58(0.85-2.94) 0.79(0.60-1.03) 1.43(0.76-2.71)AR rs2361634 0.38(0.02-6.12)PHKA1 rs3012642 0.99(0.76-1.29) 1.19(0.58-2.46) 　 0.94(0.70-1.25) 1.08(0.51-2.26)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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Table 7-1. Association of 384 SNPs with Luminal A breast cancer risk　　 Luminal A [OR(95%CI)]

Gene rs # Hetero Minor 　 Hetero MinorMTHFR rs1801131 0.92(0.67-1.27) 0.90(0.42-1.91) 0.89(0.62-1.26) 0.90(0.38-2.13)RIZ1 or PRDM2 rs2235515 0.92(0.67-1.28) 0.83(0.54-1.27) 0.85(0.59-1.21) 0.77(0.48-1.22)HSD11B1 rs4393158 0.96(0.70-1.30) 0.87(0.54-1.40) 0.97(0.69-1.36) 0.82(0.48-1.39)HSD11B1 rs17317033 2.56(0.88-7.45) 3.37(1.04-11.0)HSD11B1 rs2235543 0.97(0.71-1.33) 0.85(0.55-1.32) 1.00(0.71-1.42) 0.75(0.46-1.23)HSD11B1 rs11807619 0.97(0.71-1.34) 1.14(0.53-2.43) 0.97(0.68-1.38) 1.02(0.43-2.45)HSD11B1 rs932335 0.97(0.70-1.34) 0.71(0.27-1.86) 0.93(0.65-1.32) 0.63(0.21-1.83)2p(19150424) rs4666451 0.51(0.25-1.03) 0.52(0.24-1.08)CYP1B1 rs1800440 0.57(0.05-6.35) 0.58(0.05-6.58)CYP1B1 rs1056836 1.02(0.71-1.47) 3.47(0.69-17.31) 0.92(0.62-1.38) 2.48(0.46-13.33)ITGA6 rs17664 1.24(0.88-1.74) 1.08(0.43-2.69) 1.33(0.92-1.92) 1.37(0.48-3.94)ITGAv rs11902171 0.67(0.43-1.05) 1.08(0.15-7.72) 0.67(0.41-1.08) 1.46(0.13-17.02)BARD1 rs6759222 0.90(0.59-1.39) 0.74(0.12-4.47) 0.83(0.52-1.34) 0.27(0.03-2.69)BARD1 rs4673896 1.17(0.85-1.60) 0.97(0.62-1.51) 1.09(0.78-1.55) 0.88(0.54-1.44)BARD1 rs6717301 1.24(0.88-1.75) 0.89(0.58-1.36) 1.32(0.90-1.91) 1.06(0.66-1.69)BARD1 rs2229571 1.44(1.05-1.96) 0.83(0.51-1.35) 1.30(0.93-1.83) 0.83(0.49-1.41)BARD1 rs3768704 1.19(0.85-1.66) 0.85(0.56-1.30) 1.26(0.87-1.81) 1.02(0.64-1.62)BARD1 rs7591615 1.05(0.64-1.74) 3.44(0.36-33.21) 1.01(0.59-1.74) 1.25(0.11-14.07)BARD1 rs6435862 1.01(0.73-1.41) 0.85(0.29-2.49) 0.99(0.69-1.42) 0.71(0.23-2.24)2q35 rs13387042 0.99(0.68-1.46) 1.72(0.48-6.14) 1.09(0.72-1.66) 2.02(0.47-8.69)FGFR2 rs12505080 1.24(0.89-1.74) 1.02(0.67-1.55) 1.24(0.86-1.78) 0.97(0.61-1.54)FGFR2 rs7696175 1.03(0.73-1.44) 1.75(0.61-4.97) 1.14(0.78-1.65) 1.86(0.53-6.55)KIT rs2237038 0.69(0.50-0.95) 0.73(0.47-1.13) 0.68(0.48-0.97) 0.80(0.49-1.29)KIT rs981959 0.69(0.50-0.95) 0.71(0.46-1.09) 0.68(0.48-0.98) 0.76(0.47-1.23)KIT rs2237034 0.84(0.61-1.14) 0.73(0.38-1.43) 0.85(0.60-1.20) 0.95(0.46-1.98)KIT rs2237032 0.78(0.58-1.07) 0.80(0.46-1.40) 0.79(0.56-1.10) 0.84(0.45-1.56)KIT rs2237023 0.86(0.63-1.17) 1.01(0.62-1.63) 0.82(0.58-1.16) 0.87(0.51-1.47)KIT rs6810872 0.84(0.62-1.15) 0.98(0.61-1.59) 0.80(0.57-1.13) 0.84(0.49-1.43)KIT rs3134884 1.01(0.75-1.37) 0.93(0.44-1.98) 1.01(0.72-1.42) 0.63(0.27-1.46)KIT rs3111800 0.86(0.61-1.21) 0.92(0.60-1.40) 0.84(0.58-1.24) 0.86(0.53-1.37)KIT rs2237018 0.91(0.67-1.23) 1.03(0.59-1.79) 0.89(0.63-1.25) 1.14(0.61-2.11)KIT rs6843170 1.00(0.73-1.36) 0.97(0.55-1.73) 0.98(0.70-1.38) 1.07(0.56-2.03)KDR rs17709898 1.46(1.08-1.98) 1.12(0.61-2.08) 1.49(1.07-2.08) 1.13(0.58-2.22)KDR rs12505758 0.96(0.70-1.30) 0.50(0.24-1.04) 0.89(0.64-1.25) 0.45(0.21-0.97)KDR rs2168945 1.12(0.82-1.52) 0.82(0.51-1.32) 1.09(0.78-1.53) 0.98(0.57-1.66)KDR rs13136007 1.32(0.95-1.83) 1.28(0.83-1.95) 1.40(0.97-2.00) 1.25(0.78-2.00)KDR rs11732292 1.10(0.81-1.50) 0.81(0.50-1.30) 1.10(0.79-1.55) 0.94(0.55-1.60)KDR rs1870377 1.38(1.00-1.92) 1.20(0.78-1.84) 1.43(1.00-2.04) 1.20(0.75-1.93)KDR rs7673274 1.01(0.74-1.37) 0.57(0.29-1.11) 0.88(0.63-1.23) 0.52(0.26-1.05)KDR rs11133360 1.12(0.81-1.54) 1.22(0.79-1.87) 1.04(0.73-1.48) 1.29(0.81-2.06)STE or SULT1E1 rs3775775 1.33(0.86-2.07) 2.39(0.43-13.12) 1.18(0.73-1.92) 1.29(0.20-8.27)STE or SULT1E1 rs1881668 1.28(0.93-1.76) 1.58(1.02-2.45) 1.19(0.84-1.68) 1.47(0.91-2.38)ADH1B rs1042026 0.96(0.71-1.32) 1.23(0.53-2.85) 1.15(0.81-1.62) 1.50(0.60-3.75)5p12 rs4415084 0.90(0.65-1.26) 0.65(0.43-0.98) 0.87(0.61-1.26) 0.74(0.47-1.17)MRPS30 rs10941679 1.20(0.84-1.69) 1.44(0.96-2.16) 1.06(0.72-1.56) 1.29(0.83-2.02)5p14 rs7703618 0.75(0.55-1.03) 1.15(0.72-1.84) 0.73(0.51-1.02) 1.18(0.71-1.98)5p15 rs10035564 1.04(0.74-1.45) 0.98(0.64-1.48) 1.10(0.76-1.58) 0.94(0.59-1.49)5p(45321475bp) rs981782 0.98(0.71-1.34) 0.90(0.58-1.41) 1.12(0.79-1.58) 0.80(0.49-1.31)5q(52454339bp) rs30099 0.93(0.67-1.28) 1.18(0.76-1.85) 0.89(0.62-1.27) 1.12(0.68-1.85)MAP3K1 rs889312 1.00(0.72-1.40) 0.94(0.62-1.42) 0.91(0.63-1.32) 0.80(0.51-1.26)DHFR rs1677666 1.40(0.68-2.88) 1.53(0.72-3.27)APC rs11954856 0.78(0.56-1.08) 1.14(0.53-2.48) 0.78(0.55-1.11) 1.44(0.58-3.56)APC rs11241183 0.93(0.68-1.25) 0.94(0.55-1.59) 0.89(0.64-1.25) 0.96(0.54-1.71)APC rs2439591 0.78(0.57-1.08) 1.06(0.49-2.27) 0.78(0.55-1.10) 1.29(0.53-3.11)OR(95%CI)1:Univariate logistic regression model.

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Table 7-2 . Association of 384 SNPs with Luminal A breast cancer risk　　 Luminal A [OR(95%CI)]

Gene rs # Hetero Minor 　 Hetero MinorAPC rs2431512 0.94(0.69-1.27) 0.73(0.42-1.26) 0.98(0.70-1.37) 0.77(0.42-1.39)APC rs2431238 0.94(0.63-1.41) 0.94(0.28-3.10) 0.99(0.64-1.54) 1.35(0.29-6.27)APC rs454886 0.91(0.67-1.23) 1.10(0.67-1.82) 0.89(0.64-1.25) 1.33(0.76-2.32)APC rs501250 0.92(0.61-1.38) 1.12(0.32-3.92) 0.95(0.61-1.49) 1.87(0.33-10.57)APC rs2229992 0.96(0.70-1.30) 0.89(0.51-1.57) 0.94(0.67-1.32) 0.95(0.51-1.75)APC rs41116 0.92(0.68-1.24) 0.94(0.53-1.67) 0.90(0.65-1.27) 1.03(0.54-1.93)APC rs448475 0.90(0.66-1.21) 0.97(0.55-1.72) 0.88(0.63-1.23) 1.07(0.57-2.00)CDKN1A rs3176336 1.34(0.99-1.82) 0.72(0.40-1.31) 1.29(0.92-1.79) 0.77(0.40-1.48)CDKN1A rs1801270 0.77(0.55-1.08) 0.71(0.47-1.08) 0.77(0.53-1.12) 0.78(0.50-1.24)CCND3 rs2479717 0.96(0.64-1.45) 0.90(0.57-1.42)LSP1 rs381798 1.03(0.74-1.42) 0.89(0.58-1.37) 1.01(0.71-1.44) 0.90(0.56-1.45)ECHDC1 rs2180341 0.83(0.61-1.13) 1.11(0.64-1.93) 0.89(0.63-1.25) 1.21(0.66-2.22)ECHDC1 rs6569479 0.82(0.61-1.12) 1.10(0.63-1.91) 0.88(0.63-1.24) 1.20(0.65-2.21)ECHDC1 rs6569480 0.83(0.61-1.13) 1.10(0.63-1.92) 0.89(0.63-1.26) 1.21(0.66-2.22)ECHDC1 rs7776136 0.83(0.61-1.13) 1.11(0.64-1.93) 0.89(0.63-1.25) 1.21(0.66-2.23)ESR1 rs851984 1.19(0.83-1.69) 0.12(0.02-0.91) 1.13(0.76-1.66) 0.08(0.01-0.67)ESR1 rs851982 1.14(0.80-1.63) 0.11(0.02-0.90) 1.08(0.73-1.59) 0.08(0.01-0.66)ESR1 rs2881766 1.39(1.00-1.93) 1.51(0.99-2.31) 1.49(1.04-2.13) 1.55(0.96-2.48)ESR1 rs2077647 1.26(0.92-1.73) 1.52(0.99-2.35) 1.34(0.95-1.90) 1.56(0.96-2.53)ESR1 rs9322331 1.39(0.69-2.81) 1.25(0.59-2.66)ESR1 rs712221 1.15(0.82-1.61) 1.46(0.97-2.19) 1.20(0.84-1.73) 1.33(0.85-2.10)ESR1 rs1801132 0.89(0.63-1.27) 0.81(0.54-1.22) 0.76(0.52-1.12) 0.76(0.49-1.19)ESR1 rs3020314 1.12(0.82-1.54) 1.09(0.47-2.51) 1.21(0.85-1.72) 1.18(0.47-2.96)ESR1 rs3020377 1.11(0.81-1.52) 0.99(0.44-2.26) 1.21(0.85-1.72) 1.06(0.43-2.59)ESR1 rs3020390 0.82(0.60-1.11) 0.89(0.55-1.44) 0.92(0.66-1.30) 0.90(0.53-1.53)ESR1 rs3020317 0.82(0.59-1.15) 1.28(0.86-1.92) 0.82(0.57-1.19) 1.20(0.77-1.86)ESR1 rs3020394 0.86(0.63-1.18) 0.84(0.52-1.33) 0.99(0.70-1.38) 0.83(0.50-1.39)ESR1 rs3020396 1.15(0.82-1.61) 1.46(0.97-2.19) 0.99(0.71-1.40) 0.76(0.45-1.27)ESR1 rs3020401 0.87(0.64-1.19) 0.80(0.51-1.28) 1.00(0.71-1.41) 0.77(0.46-1.29)ESR1 rs1884051 0.77(0.55-1.07) 0.75(0.50-1.13) 0.85(0.59-1.23) 0.75(0.48-1.18)ESR1 rs1884054 0.79(0.58-1.07) 0.96(0.55-1.67) 0.91(0.65-1.27) 0.99(0.54-1.82)ESR1 rs3020405 0.79(0.58-1.08) 0.90(0.52-1.55) 0.93(0.67-1.31) 0.93(0.51-1.69)ESR1 rs726282 0.87(0.63-1.21) 1.21(0.80-1.84) 0.86(0.61-1.23) 1.12(0.71-1.76)ESR1 rs3020407 0.78(0.57-1.06) 1.06(0.64-1.76) 0.89(0.63-1.25) 1.17(0.67-2.04)ESR1 rs6905370 1.15(0.82-1.61) 1.46(0.97-2.19) 0.79(0.55-1.13) 0.65(0.40-1.05)ESR1 rs926778 1.74(1.25-2.42) 1.66(1.08-2.54) 1.95(1.35-2.81) 1.88(1.17-3.01)ESR1 rs3020366 1.00(0.73-1.38) 0.55(0.35-0.85) 0.89(0.62-1.27) 0.52(0.32-0.84)ESR1 rs2273206 1.64(1.20-2.25) 1.59(1.00-2.54) 1.74(1.23-2.45) 1.68(1.01-2.80)ESR1 rs750686 0.91(0.65-1.26) 0.56(0.36-0.86) 0.77(0.53-1.11) 0.48(0.30-0.78)ESR1 rs2228480 0.89(0.65-1.20) 0.76(0.36-1.63) 0.89(0.64-1.25) 0.88(0.37-2.09)ESR1 rs3798577 0.79(0.58-1.10) 1.15(0.75-1.77) 0.83(0.58-1.18) 1.34(0.83-2.17)ESR1 rs910416 1.15(0.82-1.61) 1.46(0.97-2.19) 1.08(0.76-1.53) 1.18(0.73-1.92)IGFBP3 rs2854744 1.57(1.15-2.15) 0.43(0.21-0.86) 1.49(1.05-2.09) 0.46(0.22-0.95)EGFR rs11770506 1.19(0.88-1.61) 0.85(0.51-1.41) 1.13(0.81-1.58) 0.71(0.40-1.27)EGFR rs4947974 0.96(0.71-1.31) 0.93(0.56-1.52) 0.94(0.67-1.32) 0.97(0.56-1.71)EGFR rs2110290 1.03(0.76-1.39) 0.88(0.52-1.49) 1.00(0.72-1.40) 0.98(0.54-1.75)EGFR rs12667668 1.32(0.97-1.79) 1.16(0.72-1.88) 1.33(0.94-1.86) 1.24(0.73-2.12)EGFR rs12718945 1.26(0.93-1.72) 1.20(0.74-1.94) 1.24(0.89-1.75) 1.28(0.75-2.18)EGFR rs6593207 1.15(0.82-1.61) 1.46(0.97-2.19) 1.40(1.00-1.96) 1.21(0.68-2.15)EGFR rs2072454 1.25(0.91-1.71) 1.08(0.68-1.71) 1.25(0.88-1.75) 0.96(0.58-1.58)EGFR rs11536635 1.03(0.75-1.42) 1.07(0.70-1.65) 1.16(0.81-1.65) 1.00(0.63-1.60)EGFR rs11977388 1.24(0.91-1.68) 0.88(0.53-1.45) 1.33(0.94-1.86) 0.79(0.46-1.36)EGFR rs10228436 1.14(0.83-1.56) 1.05(0.69-1.61) 1.22(0.86-1.73) 1.00(0.63-1.59)ABCB1 rs1045642 1.39(1.02-1.90) 1.15(0.72-1.85) 1.31(0.93-1.85) 0.96(0.56-1.62)ABCB1 rs7787082 1.21(0.87-1.70) 1.21(0.79-1.84) 1.15(0.80-1.67) 1.12(0.70-1.79)OR(95%CI)1:Univariate logistic regression model.

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Gene rs # Hetero Minor 　 Hetero MinorABCB1 rs2091766 1.15(0.82-1.61) 1.46(0.97-2.19) 1.01(0.71-1.42) 0.77(0.46-1.28)ABCB1 rs1128503 0.97(0.71-1.34) 0.71(0.46-1.10) 1.11(0.78-1.58) 0.85(0.53-1.37)ABCB1 rs1922241 0.86(0.63-1.17) 0.58(0.36-0.94) 0.98(0.70-1.38) 0.75(0.45-1.26)ABCB1 rs868755 1.10(0.80-1.51) 1.14(0.72-1.82) 1.03(0.73-1.45) 0.95(0.57-1.61)ABCB1 rs2520464 0.98(0.71-1.35) 0.66(0.42-1.03) 1.11(0.78-1.58) 0.78(0.48-1.26)ABCB1 rs1202184 1.12(0.82-1.52) 0.64(0.40-1.04) 1.17(0.83-1.65) 0.72(0.43-1.22)ABCB1 rs12535512 1.08(0.77-1.51) 1.09(0.71-1.67) 1.04(0.72-1.50) 0.97(0.60-1.56)ABCB1 rs12720464 1.15(0.82-1.61) 1.46(0.97-2.19) 1.03(0.74-1.43) 1.10(0.53-2.31)ABCB1 rs1978095 1.10(0.81-1.49) 1.00(0.50-1.99) 1.02(0.74-1.43) 1.06(0.51-2.20)CDK6 rs3757823 1.68(1.18-2.41) 1.92(1.27-2.92) 1.65(1.11-2.44) 2.02(1.28-3.18)Q129R rs662 0.79(0.58-1.08) 0.71(0.44-1.15) 0.81(0.57-1.13) 0.66(0.39-1.12)L55M rs854560 0.89(0.57-1.40) 1.12(0.07-18.01) 0.96(0.59-1.56) 1.42(0.09-23.07)FGFR2 rs17157903 1.01(0.74-1.37) 1.15(0.61-2.17) 1.14(0.81-1.59) 1.77(0.89-3.55)MET rs2237710 1.20(0.87-1.65) 0.96(0.62-1.49) 1.20(0.84-1.70) 0.90(0.56-1.46)MET rs2299437 1.15(0.82-1.61) 1.46(0.97-2.19) 1.16(0.82-1.62) 0.83(0.48-1.42)MET rs10248537 1.16(0.85-1.58) 0.94(0.58-1.52) 1.15(0.82-1.62) 0.84(0.49-1.45)MET rs38855 1.30(0.94-1.80) 1.26(0.82-1.92) 1.50(1.05-2.15) 1.19(0.74-1.89)MET rs38858 1.32(0.95-1.82) 1.25(0.81-1.91) 1.52(1.07-2.17) 1.17(0.73-1.87)MET rs13223756 1.25(0.92-1.69) 0.84(0.48-1.47) 1.36(0.97-1.90) 0.69(0.37-1.28)MET rs2299440 1.25(0.92-1.69) 0.84(0.48-1.46) 1.36(0.97-1.91) 0.69(0.37-1.27)MET rs183642 1.44(1.01-2.05) 0.91(0.60-1.37) 1.58(1.07-2.34) 0.90(0.57-1.41)MET rs41736 1.15(0.82-1.61) 1.46(0.97-2.19) 1.61(1.09-2.38) 0.91(0.58-1.42)MET rs41739 1.48(1.04-2.11) 0.93(0.62-1.41) 1.63(1.10-2.42) 0.91(0.58-1.44)TBXAS1 rs6971207 1.21(0.88-1.65) 1.62(1.01-2.58) 1.27(0.90-1.79) 1.34(0.80-2.24)FGFR1 rs2304000 1.08(0.79-1.47) 1.43(0.91-2.27) 1.14(0.81-1.61) 1.50(0.91-2.48)FGFR1 rs4647907 1.04(0.76-1.43) 1.51(0.96-2.39) 1.10(0.78-1.55) 1.60(0.97-2.64)FGFR1 rs2956724 0.92(0.68-1.25) 0.94(0.53-1.67) 0.92(0.66-1.28) 0.87(0.46-1.63)FGFR1 rs2978073 0.88(0.65-1.19) 1.00(0.57-1.75) 0.88(0.63-1.23) 0.92(0.50-1.71)FGFR1 rs6983315 0.72(0.53-0.98) 0.94(0.59-1.48) 0.64(0.45-0.90) 0.97(0.59-1.61)FGFR1 rs6987534 0.74(0.54-1.01) 0.92(0.58-1.48) 0.68(0.48-0.95) 0.95(0.57-1.58)NBS1 rs9995 1.15(0.82-1.61) 1.46(0.97-2.19) 1.05(0.74-1.49) 0.70(0.44-1.12)NBS1 or NBN rs1805787 0.56(0.14-2.27) 0.50(0.12-2.09)8q24 rs13281615 0.88(0.64-1.23) 1.06(0.70-1.63) 1.05(0.74-1.51) 1.09(0.68-1.74)MYC rs3891248 1.01(0.73-1.39) 1.04(0.67-1.61) 1.02(0.71-1.46) 1.09(0.68-1.74)CDKN2A rs3731239 0.70(0.49-0.99) 0.60(0.23-1.56) 0.66(0.45-0.98) 0.54(0.21-1.43)MCS5A6 rs2182317 0.88(0.64-1.21) 0.50(0.20-1.25) 0.93(0.65-1.33) 0.29(0.11-0.79)EHMT1 rs4634736 0.57(0.05-6.28) 0.53(0.05-6.03)FLJ45983 rs1149901 0.84(0.54-1.32) 0.74(0.12-4.44) 0.80(0.49-1.29) 0.31(0.03-3.04)GATA3 rs570613 0.73(0.53-1.00) 0.67(0.42-1.07) 0.82(0.58-1.15) 0.66(0.39-1.10)GATA3 rs422628 0.95(0.61-1.47) 2.26(0.20-25.04) 0.97(0.61-1.56) 2.37(0.20-27.68)FGFR2 rs11200014 1.23(0.90-1.67) 1.49(0.88-2.50) 1.30(0.93-1.83) 1.32(0.74-2.33)FGFR2 rs2981579 1.16(0.83-1.63) 1.56(1.03-2.37) 1.29(0.89-1.86) 1.71(1.08-2.72)FGFR2 rs1078806 1.24(0.91-1.68) 1.40(0.83-2.37) 1.30(0.93-1.82) 1.26(0.71-2.25)FGFR2 rs1219648 1.15(0.82-1.61) 1.46(0.97-2.19) 1.27(0.89-1.80) 1.59(0.98-2.57)FGFR2 rs2420946 1.41(1.02-1.94) 1.62(1.05-2.49) 1.36(0.96-1.94) 1.52(0.94-2.45)FGFR2 rs2981582 1.53(1.12-2.08) 1.14(0.69-1.89) 1.50(1.07-2.11) 1.09(0.63-1.88)FGFR2 rs10510126 1.09(0.67-1.78) 1.21(0.70-2.10)LSP1 rs661348 1.08(0.78-1.48) 1.16(0.76-1.77) 1.06(0.75-1.51) 0.98(0.61-1.55)LSP1 rs3817198 1.03(0.74-1.44) 0.63(0.21-1.91) 1.07(0.75-1.54) 0.28(0.07-1.07)H19 rs2107425 1.09(0.77-1.54) 0.91(0.59-1.39) 1.06(0.73-1.56) 0.88(0.55-1.41)CCND1 rs3212891 1.15(0.82-1.61) 1.46(0.97-2.19) 0.79(0.54-1.15) 0.87(0.22-3.36)CCND1 rs678653 0.85(0.60-1.20) 1.10(0.32-3.84) 0.85(0.58-1.25) 0.89(0.23-3.45)NUMA1 rs3750913 0.58(0.35-0.97) 1.08(0.15-7.71) 0.61(0.36-1.04) 0.96(0.13-6.98)PGR rs500760 1.03(0.76-1.41) 0.86(0.30-2.52) 1.07(0.76-1.50) 0.71(0.23-2.24)PGR rs511298 0.97(0.71-1.34) 0.97(0.32-2.91) 1.00(0.70-1.41) 0.78(0.24-2.52)OR(95%CI)1:Univariate logistic regression model.

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Table 7-4 . Association of 384 SNPs with Luminal A breast cancer risk　　 Luminal A [OR95%CI)]

Gene rs # Hetero Minor 　 Hetero MinorPGR rs1042839 9.26(1.15-74.4) 9.61(1.17-78.7)PGR rs1042838 9.34(1.16-75.0) 9.69(1.18-79.3)PGR rs660149 0.75(0.31-1.87) 0.76(0.29-2.00)PGR rs2020876 1.58(0.63-3.97) 2.09(0.73-5.95)PGR rs7116336 1.05(0.77-1.44) 0.84(0.33-2.12) 1.04(0.73-1.46) 0.92(0.36-2.36)PGR rs11571171 0.94(0.68-1.30) 1.69(0.47-6.06) 0.93(0.65-1.34) 1.60(0.44-5.86)PGR rs566351 1.19(0.86-1.63) 0.66(0.22-1.99) 1.19(0.84-1.69) 0.77(0.24-2.43)PGR rs506487 0.57(0.05-6.28) 0.66(0.06-7.72)PGR rs518162 1.03(0.43-2.46) 1.12(0.44-2.83)MMP8 rs1892886 1.31(0.88-1.95) 0.71(0.17-2.99) 1.19(0.76-1.85) 0.62(0.14-2.71)CDKN1B rs34330 0.99(0.71-1.38) 1.06(0.70-1.59) 1.04(0.72-1.49) 1.05(0.67-1.64)IGF1 rs2946834 1.14(0.81-1.60) 0.90(0.60-1.37) 1.06(0.73-1.55) 0.86(0.54-1.35)IGF1 rs5742714 1.13(0.82-1.56) 1.10(0.51-2.39) 1.00(0.70-1.43) 0.99(0.43-2.29)IGF1 rs6214 1.09(0.77-1.55) 1.12(0.75-1.67) 0.98(0.67-1.44) 0.93(0.60-1.44)IGF1 rs1520220 1.15(0.82-1.61) 1.46(0.97-2.19) 1.11(0.77-1.60) 0.89(0.56-1.40)IGF1 rs10745940 1.21(0.87-1.68) 0.94(0.62-1.43) 1.12(0.77-1.61) 0.90(0.57-1.42)IGF1 rs5742694 1.13(0.81-1.56) 1.10(0.51-2.38) 1.04(0.72-1.48) 0.91(0.38-2.14)IGF1 rs978458 1.19(0.85-1.65) 0.96(0.64-1.45) 1.09(0.76-1.57) 0.93(0.59-1.47)IGF1 rs5742667 1.17(0.84-1.64) 0.92(0.61-1.40) 1.10(0.76-1.59) 0.90(0.57-1.42)IGF1 rs2373721 1.10(0.80-1.52) 1.27(0.59-2.76) 0.97(0.68-1.39) 1.16(0.51-2.68)IGF1 rs7136446 1.14(0.83-1.57) 1.39(0.65-2.98) 0.97(0.68-1.39) 1.17(0.51-2.70)IGF1 rs9989002 1.15(0.82-1.61) 1.46(0.97-2.19) 0.76(0.52-1.10) 1.09(0.42-2.83)IGF1 rs5742632 1.06(0.76-1.46) 0.69(0.45-1.06) 0.99(0.69-1.42) 0.63(0.39-1.01)IGF1 rs2195240 1.05(0.76-1.45) 0.70(0.46-1.07) 0.98(0.69-1.41) 0.67(0.42-1.07)IGF1 rs5742629 1.08(0.78-1.49) 0.71(0.46-1.09) 1.02(0.72-1.46) 0.67(0.42-1.07)IGF1 rs7956547 0.94(0.67-1.32) 1.01(0.40-2.52) 0.78(0.53-1.13) 0.83(0.30-2.28)IGF1 rs4764698 0.94(0.70-1.28) 0.67(0.37-1.19) 1.07(0.76-1.49) 0.68(0.36-1.27)IGF1 rs10778176 1.16(0.84-1.60) 0.67(0.44-1.03) 1.10(0.77-1.58) 0.65(0.41-1.04)IGF1 rs2162679 1.15(0.82-1.61) 1.46(0.97-2.19) 1.06(0.75-1.50) 1.08(0.66-1.78)IGF1 rs35765 1.94(1.18-3.19) 0.40(0.04-3.89) 2.04(1.20-3.47) 0.53(0.05-5.35)IGF1 rs7965399 0.88(0.65-1.19) 0.96(0.55-1.70) 0.90(0.65-1.26) 1.01(0.55-1.85)IGF1 rs855211 0.96(0.71-1.30) 1.13(0.69-1.87) 1.01(0.72-1.42) 1.22(0.72-2.07)BRCA2 rs144848 0.97(0.72-1.31) 1.33(0.69-2.58) 0.96(0.69-1.34) 1.43(0.67-3.03)BRCA2 rs4942485 0.91(0.46-1.79) 0.77(0.36-1.62)IRS2 rs9515118 1.17(0.86-1.58) 0.53(0.28-1.00) 1.23(0.88-1.72) 0.53(0.27-1.06)IRS2 rs4773082 1.15(0.82-1.61) 1.46(0.97-2.19) 0.96(0.69-1.33) 0.93(0.46-1.86)IRS2 rs2289046 1.10(0.78-1.55) 1.23(0.82-1.86) 1.09(0.75-1.59) 1.28(0.81-2.01)IRS2 rs754204 0.97(0.71-1.31) 1.26(0.73-2.17) 0.90(0.64-1.25) 1.35(0.73-2.47)IRS2 rs7987237 1.01(0.74-1.37) 0.48(0.23-1.01) 1.04(0.74-1.45) 0.48(0.22-1.06)IRS2 rs12584136 1.12(0.68-1.87) 1.25(0.72-2.15)IRS2 rs9559648 1.10(0.81-1.49) 0.93(0.41-2.09) 1.03(0.73-1.43) 0.88(0.35-2.22)IRS2 rs9559654 1.23(0.90-1.67) 1.23(0.52-2.88) 1.14(0.81-1.60) 1.24(0.48-3.18)IRS2 rs7997595 1.03(0.76-1.40) 0.38(0.18-0.76) 0.97(0.70-1.36) 0.40(0.19-0.87)IRS2 rs7981705 0.78(0.40-1.50) 0.88(0.43-1.82)IRS2 rs4773092 1.21(0.86-1.71) 0.99(0.65-1.49) 1.23(0.85-1.80) 1.10(0.70-1.73)ESR2 rs1255998 1.05(0.75-1.46) 1.27(0.85-1.90) 1.08(0.75-1.56) 1.36(0.87-2.14)ESR2 rs8018687 1.15(0.82-1.61) 1.46(0.97-2.19) 1.16(0.75-1.79) 0.34(0.03-3.43)ESR2 rs928554 0.90(0.66-1.22) 0.82(0.52-1.30) 0.85(0.61-1.20) 0.90(0.54-1.50)ESR2 rs1152579 0.92(0.68-1.26) 0.77(0.48-1.22) 0.88(0.63-1.23) 0.85(0.51-1.43)ESR2 rs1256049 1.02(0.75-1.39) 1.65(0.96-2.82) 1.09(0.78-1.52) 1.80(1.00-3.25)ESR2 rs1256030 0.88(0.64-1.21) 0.93(0.60-1.45) 0.80(0.57-1.13) 1.04(0.64-1.70)ESR2 rs1271572 0.88(0.64-1.21) 0.96(0.62-1.50) 0.81(0.57-1.15) 1.06(0.65-1.74)XRCC3 rs861539 1.03(0.60-1.77) 0.98(0.53-1.80)XRCC3 rs1799796 1.15(0.82-1.61) 1.46(0.97-2.19) 0.89(0.64-1.25) 0.83(0.48-1.44)XRCC3 rs1799794 1.19(0.84-1.70) 1.12(0.75-1.69) 1.04(0.70-1.54) 1.05(0.67-1.65)OR(95%CI)1:Univariate logistic regression model.

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Gene rs # Hetero Minor 　 Hetero MinorAKT1 rs2494744 1.09(0.80-1.49) 1.28(0.82-2.00) 1.02(0.72-1.43) 1.26(0.76-2.08)AKT1 rs2498787 0.94(0.69-1.28) 1.20(0.77-1.87) 0.90(0.64-1.27) 1.20(0.73-1.98)CYP20 rs4646 1.02(0.75-1.38) 1.03(0.62-1.70) 1.02(0.73-1.43) 1.08(0.62-1.87)CYP19 rs10046 0.96(0.69-1.35) 1.03(0.68-1.55) 0.96(0.66-1.39) 1.03(0.66-1.63)CYP21 rs727479 0.92(0.67-1.24) 0.96(0.59-1.57) 0.92(0.65-1.29) 1.01(0.60-1.71)MAP2K1 rs7174378 1.15(0.82-1.61) 1.46(0.97-2.19) 1.02(0.71-1.47) 0.83(0.52-1.32)MAP2K1 rs7181936 1.09(0.80-1.49) 1.01(0.64-1.59) 1.15(0.82-1.63) 1.04(0.63-1.71)MAP2K1 rs28620576 1.06(0.78-1.44) 1.10(0.64-1.90) 1.31(0.94-1.83) 1.02(0.56-1.86)MAP2K1 rs8039880 1.05(0.76-1.45) 0.74(0.47-1.15) 1.08(0.76-1.54) 0.79(0.49-1.29)CYP1A1 rs1048943 1.16(0.85-1.58) 1.69(0.86-3.30) 1.32(0.94-1.86) 1.61(0.76-3.39)IGF1R rs4966007 1.14(0.83-1.58) 1.60(1.06-2.43) 1.26(0.88-1.80) 1.84(1.16-2.92)IGF1R rs8028620 1.27(0.90-1.81) 1.23(0.82-1.85) 1.42(0.97-2.09) 1.38(0.88-2.16)IGF1R rs4966009 1.15(0.82-1.61) 1.46(0.97-2.19) 1.24(0.87-1.77) 1.78(1.12-2.85)IGF1R rs8027457 1.28(0.91-1.82) 1.21(0.81-1.82) 1.43(0.98-2.10) 1.33(0.85-2.08)IGF1R rs4966012 0.82(0.61-1.11) 0.71(0.40-1.26) 0.75(0.54-1.04) 0.66(0.36-1.24)IGF1R rs1574213 1.00(0.73-1.36) 1.14(0.49-2.68) 0.93(0.66-1.30) 1.00(0.39-2.59)IGF1R rs11630479 0.81(0.60-1.10) 0.73(0.41-1.30) 0.79(0.56-1.10) 0.65(0.34-1.23)IGF1R rs4966013 0.76(0.55-1.06) 0.82(0.55-1.23) 0.85(0.59-1.23) 0.82(0.52-1.27)IGF1R rs4966015 1.05(0.77-1.42) 1.75(0.92-3.34) 1.02(0.73-1.42) 1.73(0.86-3.48)IGF1R rs8032477 1.15(0.82-1.61) 1.46(0.97-2.19) 0.94(0.64-1.36) 0.61(0.39-0.96)IGF1R rs11634241 0.76(0.56-1.04) 0.93(0.56-1.53) 0.83(0.59-1.16) 0.82(0.47-1.43)IGF1R rs932071 0.81(0.60-1.11) 0.57(0.27-1.22) 0.89(0.63-1.25) 0.41(0.18-0.98)IGF1R rs875686 0.77(0.57-1.05) 0.61(0.31-1.19) 0.84(0.60-1.17) 0.56(0.26-1.18)IGF1R rs1567811 0.94(0.69-1.29) 0.74(0.47-1.17) 1.09(0.77-1.53) 0.70(0.42-1.18)IGF1R rs11632952 0.79(0.58-1.08) 0.79(0.40-1.55) 0.93(0.66-1.30) 0.51(0.24-1.10)IGF1R rs4966024 0.83(0.59-1.17) 0.87(0.58-1.31) 0.98(0.67-1.44) 0.89(0.56-1.40)IGF1R rs8041224 1.15(0.82-1.61) 1.46(0.97-2.19) 0.94(0.66-1.34) 0.70(0.43-1.13)IGF1R rs7175052 0.87(0.64-1.20) 0.72(0.47-1.11) 0.97(0.68-1.37) 0.68(0.42-1.11)IGF1R rs2137680 0.90(0.64-1.27) 0.85(0.57-1.27) 1.06(0.72-1.54) 0.87(0.56-1.35)IGF1R rs12439557 0.86(0.63-1.17) 0.60(0.34-1.04) 0.99(0.71-1.40) 0.47(0.25-0.89)IGF1R rs4966028 1.01(0.72-1.42) 1.50(0.65-3.48) 0.96(0.66-1.40) 1.92(0.77-4.80)IGF1R rs907806 0.99(0.71-1.38) 1.81(0.69-4.74) 0.95(0.65-1.37) 2.72(0.92-8.10)IGF1R rs8041953 0.94(0.68-1.31) 1.51(0.63-3.65) 0.91(0.63-1.31) 2.10(0.80-5.52)IGF1R rs2670501 1.15(0.82-1.61) 1.46(0.97-2.19) 0.96(0.68-1.37) 0.82(0.50-1.33)IGF1R rs4246340 1.05(0.75-1.46) 1.22(0.80-1.87) 1.02(0.70-1.47) 1.11(0.70-1.76)IGF1R rs2684777 0.80(0.58-1.10) 0.84(0.54-1.32) 0.87(0.62-1.24) 0.85(0.52-1.39)IGF1R rs8030950 1.05(0.77-1.43) 1.06(0.58-1.95) 1.06(0.75-1.49) 1.01(0.52-1.95)IGF1R rs12594847 1.00(0.73-1.38) 1.29(0.84-2.00) 1.10(0.78-1.56) 1.22(0.76-1.98)IGF1R rs2684781 1.01(0.73-1.38) 1.19(0.78-1.83) 1.09(0.77-1.55) 1.10(0.69-1.76)IGF1R rs1521481 1.08(0.80-1.47) 0.90(0.49-1.64) 1.07(0.76-1.49) 0.86(0.45-1.67)IGF1R rs4966035 1.15(0.82-1.61) 1.46(0.97-2.19) 0.78(0.54-1.14) 0.88(0.56-1.38)IGF1R rs4966036 0.83(0.60-1.13) 0.83(0.53-1.31) 0.92(0.65-1.30) 0.87(0.52-1.44)IGF1R rs7165875 0.88(0.62-1.24) 1.04(0.70-1.57) 0.79(0.54-1.16) 0.93(0.59-1.46)IGF1R rs3743259 0.84(0.60-1.20) 1.13(0.75-1.69) 0.78(0.53-1.14) 1.00(0.64-1.58)IGF1R rs3743260 1.16(0.83-1.63) 1.30(0.56-2.99) 1.21(0.83-1.76) 1.35(0.56-3.25)IGF1R rs2684810 1.14(0.84-1.54) 1.14(0.67-1.93) 1.06(0.76-1.48) 0.98(0.55-1.77)IGF1R rs4966039 0.98(0.71-1.35) 0.97(0.44-2.14) 0.85(0.60-1.21) 0.91(0.40-2.08)IGF1R rs2684805 1.15(0.82-1.61) 1.46(0.97-2.19) 1.46(1.01-2.11) 1.56(0.98-2.48)IGF1R rs2684803 1.59(1.16-2.17) 1.28(0.80-2.05) 1.66(1.18-2.35) 1.21(0.73-2.01)IGF1R rs1546713 1.58(1.16-2.16) 1.24(0.77-2.00) 1.66(1.18-2.35) 1.21(0.73-2.01)IGF1R rs7166558 1.63(1.19-2.22) 1.33(0.83-2.13) 1.71(1.21-2.42) 1.27(0.77-2.11)IGF1R rs2229765 1.62(1.19-2.22) 1.35(0.84-2.17) 1.73(1.22-2.44) 1.30(0.78-2.16)IGF1R rs11635251 0.88(0.65-1.19) 0.40(0.22-0.72) 0.86(0.62-1.20) 0.30(0.16-0.59)IGF1R rs8038056 1.21(0.89-1.64) 0.87(0.53-1.42) 1.35(0.96-1.89) 0.91(0.52-1.59)IGF1R rs12916884 1.15(0.82-1.61) 1.46(0.97-2.19) 0.87(0.62-1.21) 0.31(0.17-0.58)OR(95%CI)1:Univariate logistic regression model.

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Gene rs # Hetero Minor 　 Hetero MinorIGF1R rs7173377 1.30(0.95-1.77) 1.09(0.68-1.74) 1.38(0.98-1.94) 1.14(0.68-1.93)IGF1R rs7166565 1.32(0.97-1.80) 1.06(0.66-1.69) 1.43(1.02-2.01) 1.12(0.67-1.89)IGF1R rs939626 0.97(0.71-1.33) 0.66(0.37-1.19) 1.01(0.72-1.42) 0.69(0.35-1.34)IGF1R rs12437963 1.35(0.98-1.86) 1.35(0.86-2.11) 1.41(0.99-2.00) 1.40(0.87-2.27)IGF1R rs2684788 1.04(0.74-1.47) 1.21(0.80-1.82) 1.08(0.74-1.57) 1.26(0.81-1.97)IGF1R rs1815009 1.21(0.86-1.70) 1.23(0.82-1.84) 1.28(0.88-1.86) 1.30(0.84-2.02)A2BP1 rs7203563 1.15(0.82-1.61) 1.46(0.97-2.19) 0.88(0.62-1.25) 0.89(0.34-2.28)TNRC9/LOC643714 rs8051542 1.28(0.94-1.73) 1.07(0.48-2.36) 1.13(0.81-1.58) 0.81(0.33-1.99)TNRC9/LOC643714 rs12443621 1.16(0.85-1.58) 0.96(0.59-1.56) 1.19(0.85-1.67) 1.04(0.61-1.76)TNRC9 or TOX3 rs3803662 0.66(0.48-0.91) 0.66(0.42-1.03) 0.72(0.51-1.01) 0.70(0.43-1.15)ATP1B2 rs1641512 1.04(0.76-1.42) 0.62(0.39-0.99) 1.07(0.76-1.50) 0.72(0.43-1.19)TP53 rs9894946 1.24(0.71-2.17) 1.08(0.59-1.97)TP53 rs1614984 0.86(0.63-1.17) 0.78(0.48-1.26) 0.84(0.60-1.18) 0.96(0.56-1.65)TP53 rs1042522 0.81(0.59-1.11) 0.78(0.49-1.22) 0.77(0.55-1.09) 0.86(0.52-1.43)WDR79 rs2287499 0.81(0.60-1.10) 0.69(0.34-1.39) 0.73(0.52-1.02) 0.71(0.32-1.56)WDR79 rs17885803 0.86(0.58-1.27) 3.36(0.67-16.76) 0.87(0.57-1.35) 3.92(0.77-19.83)WDR79 rs2287498 0.82(0.60-1.11) 0.69(0.34-1.39) 0.74(0.53-1.03) 0.71(0.32-1.57)HER2 rs1565923 1.14(0.83-1.58) 1.34(0.86-2.08) 1.14(0.79-1.62) 1.32(0.82-2.14)ERBB rs1810132 1.16(0.84-1.60) 1.33(0.85-2.06) 1.16(0.81-1.65) 1.31(0.81-2.13)HER2 rs3809717 1.14(0.84-1.54) 0.90(0.49-1.64) 1.16(0.83-1.61) 0.79(0.41-1.52)ITGB3 rs3809865 1.16(0.85-1.57) 1.13(0.54-2.34) 1.09(0.77-1.52) 1.21(0.55-2.66)ITGA3 rs1062484 0.45(0.09-2.34) 0.46(0.08-2.65)AXIN2 rs7210356 0.97(0.68-1.38) 0.94(0.40-2.21) 0.96(0.65-1.41) 0.85(0.33-2.21)AXIN2 rs4791171 0.99(0.72-1.35) 0.93(0.59-1.47) 0.90(0.63-1.27) 0.82(0.50-1.35)AXIN2 rs11079571 1.08(0.80-1.47) 1.02(0.58-1.78) 1.07(0.77-1.50) 1.25(0.66-2.37)AXIN2 rs3923087 1.05(0.77-1.43) 1.10(0.69-1.76) 0.97(0.69-1.37) 1.06(0.63-1.76)AXIN2 rs3923086 0.95(0.69-1.32) 0.78(0.29-2.09) 0.95(0.67-1.36) 0.92(0.33-2.55)GPX4 rs4807542 1.09(0.79-1.49) 0.42(0.17-1.02) 1.08(0.76-1.53) 0.59(0.23-1.51)MAP2K2 rs350916 1.15(0.82-1.61) 1.46(0.97-2.19) 1.08(0.77-1.52) 0.57(0.33-0.98)MAP2K2 rs350913 1.15(0.85-1.56) 0.57(0.34-0.95) 1.21(0.86-1.70) 0.54(0.32-0.93)MAP2K2 rs7258366 1.42(1.04-1.92) 0.86(0.50-1.48) 1.55(1.10-2.17) 0.90(0.51-1.59)MAP2K2 rs350894 1.10(0.80-1.51) 1.08(0.69-1.68) 1.32(0.93-1.88) 1.13(0.70-1.83)MAP2K2 rs12459484 1.42(1.04-1.94) 1.06(0.67-1.67) 1.58(1.11-2.23) 1.03(0.63-1.70)ICAM5 rs1056538 1.03(0.76-1.40) 1.10(0.66-1.83) 0.96(0.68-1.34) 0.96(0.55-1.66)CCNE1 rs997669 1.10(0.73-1.64) 1.45(0.39-5.44) 1.09(0.70-1.70) 1.57(0.34-7.19)XRCC1 rs25487 1.15(0.82-1.61) 1.46(0.97-2.19) 0.95(0.67-1.33) 1.51(0.74-3.08)PTGIS rs6095541 0.87(0.58-1.31) 4.49(0.50-40.41) 0.88(0.56-1.39) 3.22(0.36-29.23)PTGIS rs6095543 0.98(0.70-1.36) 0.91(0.35-2.34) 0.92(0.64-1.32) 0.90(0.32-2.54)PTGIS rs693649 1.14(0.83-1.57) 1.02(0.66-1.58) 1.10(0.78-1.56) 1.20(0.74-1.95)AURKA rs8173 0.95(0.69-1.29) 1.72(1.06-2.77) 0.90(0.64-1.26) 1.65(0.98-2.79)AURKA rs10485805 0.89(0.66-1.21) 1.35(0.66-2.74) 0.84(0.60-1.18) 1.36(0.63-2.95)AURKA rs6024840 1.00(0.74-1.36) 0.77(0.46-1.29) 1.06(0.76-1.48) 0.75(0.43-1.31)AURKA rs911160 1.15(0.82-1.61) 1.46(0.97-2.19) 1.03(0.74-1.45) 0.76(0.44-1.31)AURKA rs2298016 0.97(0.72-1.32) 0.73(0.44-1.19) 0.99(0.71-1.39) 0.69(0.40-1.18)AURKA rs2273535 1.00(0.74-1.37) 0.73(0.44-1.19) 1.01(0.72-1.42) 0.68(0.40-1.18)COMT rs4680 0.83(0.61-1.12) 0.96(0.53-1.76) 0.85(0.61-1.19) 0.90(0.45-1.78)CHEK2 rs9608698 0.90(0.67-1.22) 0.92(0.40-2.10) 0.84(0.60-1.16) 0.71(0.29-1.73)PHKA1 rs3012642 0.92(0.66-1.28) 1.00(0.40-2.50) 　 0.83(0.57-1.19) 0.87(0.33-2.29)OR(95%CI)1:Univariate logistic regression model.

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　　 LuminalB (additive model)Hetero Minor Hetero Minor


MTHFR rs1801131 0.93(0.65-1.33) 0.83(0.35-1.99) 0.99(0.67-1.46) 0.88(0.34-2.30)RIZ1 or PRDM2 rs2235515 1.03(0.72-1.49) 0.90(0.56-1.46) 1.03(0.69-1.54) 0.88(0.52-1.51)HSD11B1 rs4393158 0.84(0.59-1.19) 0.71(0.41-1.24) 0.87(0.59-1.27) 0.78(0.42-1.42)HSD11B1 rs17317033 2.80(0.91-8.67) 2.99(0.85-10.58)HSD11B1 rs2235543 0.71(0.50-1.01) 0.63(0.38-1.05) 0.65(0.44-0.96) 0.66(0.38-1.14)HSD11B1 rs11807619 0.87(0.60-1.24) 0.46(0.15-1.42) 1.04(0.70-1.54) 0.56(0.17-1.82)HSD11B1 rs932335 0.90(0.62-1.29) 0.44(0.12-1.62) 1.01(0.68-1.52) 0.54(0.14-2.05)2p(19150424) rs4666451 0.78(0.39-1.57) 0.71(0.33-1.56)CYP1B1 rs1800440 2.59(0.43-15.6) 1.55(0.21-11.28)CYP1B1 rs1056836 1.01(0.67-1.52) 1.72(0.24-12.31) 0.96(0.61-1.50) 1.40(0.19-10.2)ITGA6 rs17664 0.75(0.50-1.14) 1.47(0.59-3.70) 0.75(0.47-1.18) 2.06(0.73-5.83)ITGAv rs11902171 0.90(0.56-1.44) 0.84(0.08-9.35) 0.98(0.59-1.63) 1.67(0.10-28.0)BARD1 rs6759222 1.03(0.64-1.66) 1.14(0.19-6.87) 1.05(0.63-1.76) 1.09(0.17-6.85)BARD1 rs4673896 0.97(0.68-1.38) 0.84(0.51-1.39) 0.91(0.62-1.34) 0.76(0.43-1.32)BARD1 rs6717301 0.97(0.67-1.42) 0.81(0.51-1.30) 0.98(0.65-1.49) 0.99(0.59-1.65)BARD1 rs2229571 1.25(0.88-1.77) 0.80(0.46-1.39) 1.17(0.80-1.72) 0.73(0.40-1.36)BARD1 rs3768704 0.94(0.65-1.37) 0.81(0.50-1.29) 0.94(0.63-1.42) 0.94(0.56-1.57)BARD1 rs7591615 0.61(0.32-1.18) 0.54(0.26-1.13)BARD1 rs6435862 1.38(0.96-1.98) 1.42(0.48-4.17) 1.29(0.87-1.92) 1.18(0.37-3.72)2q35 rs13387042 1.09(0.71-1.66) 1.31(0.29-5.91) 1.16(0.73-1.86) 1.94(0.38-10.0)FGFR2 rs12505080 1.21(0.83-1.78) 1.20(0.75-1.91) 1.40(0.91-2.15) 1.34(0.80-2.24)FGFR2 rs7696175 0.90(0.61-1.33) 1.69(0.54-5.32) 0.96(0.62-1.48) 1.66(0.43-6.34)KIT rs2237038 0.97(0.68-1.40) 0.78(0.47-1.30) 0.94(0.63-1.40) 0.73(0.41-1.29)KIT rs981959 0.97(0.67-1.40) 0.71(0.42-1.20) 0.93(0.62-1.40) 0.64(0.35-1.16)KIT rs2237034 0.79(0.56-1.13) 0.97(0.48-1.94) 0.68(0.45-1.01) 1.03(0.47-2.26)KIT rs2237032 0.96(0.68-1.35) 0.95(0.51-1.77) 0.78(0.53-1.15) 0.90(0.45-1.81)KIT rs2237023 1.28(0.90-1.82) 1.17(0.67-2.04) 1.39(0.93-2.06) 1.02(0.55-1.92)KIT rs6810872 1.27(0.89-1.81) 1.17(0.67-2.04) 1.38(0.93-2.05) 1.03(0.55-1.93)KIT rs3134884 1.41(1.01-1.98) 0.85(0.34-2.13) 1.55(1.07-2.25) 0.63(0.22-1.80)KIT rs3111800 1.44(0.95-2.20) 1.67(1.02-2.73) 1.52(0.95-2.45) 1.59(0.91-2.77)KIT rs2237018 1.36(0.97-1.90) 0.86(0.43-1.72) 1.30(0.89-1.89) 0.71(0.31-1.61)KIT rs6843170 1.34(0.96-1.89) 0.96(0.49-1.90) 1.34(0.92-1.95) 0.76(0.33-1.74)KDR rs17709898 1.25(0.89-1.76) 0.82(0.39-1.71) 1.12(0.76-1.63) 0.83(0.37-1.84)KDR rs12505758 0.81(0.56-1.15) 0.65(0.30-1.40) 0.64(0.43-0.95) 0.62(0.28-1.36)KDR rs2168945 1.15(0.81-1.64) 1.03(0.61-1.72) 1.17(0.79-1.73) 1.24(0.69-2.22)KDR rs13136007 1.26(0.87-1.83) 1.18(0.73-1.92) 1.39(0.92-2.11) 1.22(0.71-2.10)KDR rs11732292 1.15(0.81-1.63) 1.04(0.62-1.74) 1.20(0.81-1.77) 1.24(0.69-2.23)KDR rs1870377 1.28(0.89-1.86) 1.27(0.79-2.03) 1.41(0.93-2.12) 1.35(0.80-2.29)KDR rs7673274 0.83(0.58-1.18) 0.58(0.27-1.23) 0.65(0.43-0.96) 0.55(0.25-1.20)KDR rs11133360 1.44(1.00-2.07) 1.41(0.86-2.30) 1.44(0.96-2.15) 1.39(0.80-2.42)STE or SULT1E1 rs3775775 0.79(0.45-1.37) 0.84(0.08-9.37) 0.61(0.33-1.14)STE or SULT1E1 rs1881668 1.05(0.74-1.49) 1.07(0.64-1.79) 0.90(0.61-1.33) 0.94(0.53-1.66)ADH1B rs1042026 0.99(0.70-1.40) 0.93(0.34-2.57) 1.13(0.77-1.66) 1.00(0.32-3.11)5p12 rs4415084 0.96(0.66-1.39) 0.57(0.35-0.92) 1.11(0.74-1.67) 0.65(0.38-1.11)MRPS30 rs10941679 1.18(0.80-1.74) 1.34(0.85-2.11) 1.13(0.73-1.75) 1.19(0.71-1.98)5p14 rs7703618 1.02(0.72-1.44) 0.76(0.42-1.38) 1.18(0.81-1.73) 0.61(0.30-1.26)5p15 rs10035564 0.94(0.65-1.36) 0.79(0.49-1.28) 0.87(0.58-1.31) 0.80(0.48-1.35)5p(45321475bp) rs981782 1.11(0.76-1.60) 1.72(1.08-2.74) 1.17(0.78-1.77) 1.81(1.09-3.01)5q(52454339bp) rs30099 0.80(0.56-1.15) 0.70(0.41-1.20) 0.81(0.54-1.19) 0.73(0.40-1.31)MAP3K1 rs889312 1.02(0.70-1.49) 1.04(0.65-1.66) 1.02(0.67-1.57) 0.93(0.55-1.55)DHFR rs1677666 1.76(0.82-3.76) 1.77(0.79-3.98)APC rs11954856 0.87(0.61-1.25) 0.37(0.10-1.32) 0.77(0.51-1.15) 0.54(0.14-2.11)APC rs11241183 0.97(0.69-1.36) 0.66(0.34-1.27) 1.01(0.69-1.47) 0.68(0.33-1.38)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model.Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

Table 8-1 . Association of 384 SNPs with Luminal B breast cancer risk

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Table 8-2 . Association of 384 SNPs with Luminal B breast cancer risk　　 LuminalB (additive model)


APC rs2439591 0.85(0.59-1.21) 0.69(0.26-1.84) 0.75(0.50-1.12) 0.93(0.32-2.68)APC rs2431512 1.00(0.71-1.41) 1.07(0.60-1.89) 1.18(0.81-1.73) 1.15(0.62-2.13)APC rs2431238 1.26(0.82-1.92) 0.59(0.12-2.95) 1.42(0.89-2.27) 1.19(0.19-7.35)APC rs454886 1.28(0.91-1.80) 1.04(0.57-1.89) 1.46(1.00-2.14) 1.09(0.55-2.14)APC rs501250 1.21(0.78-1.87) 0.71(0.14-3.68) 1.31(0.81-2.11) 1.58(0.22-11.5)APC rs2229992 1.03(0.73-1.45) 0.71(0.36-1.41) 1.09(0.75-1.59) 0.75(0.36-1.57)APC rs41116 1.02(0.73-1.44) 0.67(0.32-1.38) 1.08(0.74-1.57) 0.73(0.33-1.61)APC rs448475 1.02(0.72-1.43) 0.79(0.39-1.57) 1.07(0.73-1.56) 0.86(0.41-1.82)CDKN1A rs3176336 1.21(0.86-1.71) 1.32(0.74-2.35) 1.31(0.89-1.94) 1.68(0.89-3.16)CDKN1A rs1801270 0.90(0.61-1.33) 0.96(0.60-1.53) 0.81(0.53-1.25) 0.86(0.51-1.45)CCND3 rs2479717 0.78(0.48-1.27) 0.72(0.41-1.24)LSP1 rs381798 1.20(0.82-1.74) 1.26(0.78-2.02) 1.18(0.78-1.79) 1.30(0.77-2.20)ECHDC1 rs2180341 0.99(0.70-1.39) 1.51(0.84-2.73) 1.14(0.77-1.67) 1.75(0.91-3.38)ECHDC1 rs6569479 0.98(0.70-1.39) 1.51(0.83-2.72) 1.13(0.77-1.66) 1.74(0.90-3.36)ECHDC1 rs6569480 0.99(0.70-1.40) 1.51(0.84-2.73) 1.15(0.78-1.69) 1.75(0.91-3.38)ECHDC1 rs7776136 0.99(0.70-1.39) 1.52(0.84-2.74) 1.13(0.77-1.66) 1.76(0.92-3.40)ESR1 rs851984 0.83(0.54-1.27) 0.66(0.20-2.12) 0.79(0.49-1.26) 0.54(0.16-1.82)ESR1 rs851982 0.78(0.51-1.20) 0.82(0.27-2.42) 0.74(0.46-1.19) 0.66(0.22-2.03)ESR1 rs2881766 1.03(0.72-1.47) 0.97(0.60-1.57) 1.10(0.74-1.64) 1.03(0.60-1.77)ESR1 rs2077647 1.19(0.84-1.69) 1.18(0.71-1.95) 1.32(0.89-1.95) 1.19(0.67-2.09)ESR1 rs9322331 1.51(0.71-3.24) 1.23(0.53-2.85)ESR1 rs712221 1.09(0.75-1.60) 1.51(0.96-2.38) 1.07(0.71-1.62) 1.40(0.84-2.33)ESR1 rs1801132 0.99(0.67-1.47) 0.85(0.53-1.36) 1.05(0.67-1.65) 0.87(0.51-1.47)ESR1 rs3020314 1.13(0.80-1.61) 0.74(0.25-2.13) 1.22(0.82-1.81) 0.96(0.31-2.94)ESR1 rs3020377 1.15(0.81-1.64) 0.68(0.24-1.95) 1.23(0.83-1.83) 0.86(0.28-2.59)ESR1 rs3020390 1.16(0.82-1.64) 0.93(0.53-1.64) 1.17(0.80-1.72) 0.97(0.52-1.79)ESR1 rs3020317 0.95(0.65-1.38) 0.98(0.61-1.58) 1.02(0.67-1.55) 1.07(0.64-1.78)ESR1 rs3020394 1.09(0.77-1.54) 0.98(0.57-1.65) 1.11(0.75-1.64) 1.00(0.56-1.78)ESR1 rs3020396 1.15(0.82-1.61) 1.46(0.97-2.19) 1.06(0.72-1.56) 0.91(0.51-1.61)ESR1 rs3020401 1.08(0.76-1.53) 0.94(0.56-1.59) 1.06(0.72-1.56) 0.93(0.52-1.65)ESR1 rs1884051 1.09(0.74-1.60) 0.82(0.51-1.32) 0.97(0.64-1.47) 0.74(0.44-1.25)ESR1 rs1884054 1.20(0.85-1.68) 0.86(0.44-1.68) 1.28(0.88-1.87) 0.76(0.36-1.62)ESR1 rs3020405 1.24(0.88-1.74) 0.87(0.45-1.68) 1.33(0.91-1.94) 0.80(0.39-1.67)ESR1 rs726282 1.04(0.73-1.49) 0.78(0.46-1.30) 1.07(0.72-1.59) 0.78(0.45-1.37)ESR1 rs3020407 1.19(0.84-1.67) 0.83(0.44-1.58) 1.26(0.87-1.84) 0.79(0.39-1.62)ESR1 rs6905370 1.15(0.82-1.61) 1.46(0.97-2.19) 0.88(0.58-1.34) 0.81(0.47-1.39)ESR1 rs926778 1.46(1.01-2.09) 0.97(0.58-1.61) 1.52(1.02-2.27) 1.12(0.64-1.95)ESR1 rs3020366 1.51(1.04-2.19) 0.72(0.43-1.21) 1.25(0.83-1.89) 0.67(0.38-1.18)ESR1 rs2273206 1.37(0.97-1.94) 0.73(0.40-1.34) 1.37(0.94-2.01) 0.73(0.38-1.42)ESR1 rs750686 1.18(0.81-1.72) 0.71(0.43-1.16) 0.98(0.65-1.49) 0.69(0.40-1.18)ESR1 rs2228480 0.76(0.53-1.07) 0.36(0.12-1.08) 0.77(0.52-1.13) 0.48(0.15-1.55)ESR1 rs3798577 0.62(0.44-0.88) 0.59(0.35-1.00) 0.62(0.42-0.92) 0.53(0.29-0.98)ESR1 rs910416 1.15(0.82-1.61) 1.46(0.97-2.19) 0.91(0.62-1.34) 0.34(0.17-0.69)IGFBP3 rs2854744 1.07(0.74-1.54) 0.57(0.28-1.15) 0.94(0.63-1.41) 0.54(0.26-1.16)EGFR rs11770506 0.80(0.56-1.13) 0.58(0.32-1.05) 0.77(0.53-1.13) 0.60(0.31-1.17)EGFR rs4947974 1.01(0.72-1.43) 1.03(0.59-1.79) 0.98(0.67-1.44) 1.12(0.60-2.07)EGFR rs2110290 1.08(0.77-1.52) 0.95(0.53-1.70) 1.08(0.73-1.58) 1.04(0.54-2.01)EGFR rs12667668 1.19(0.85-1.68) 0.76(0.42-1.37) 1.15(0.79-1.69) 0.75(0.38-1.46)EGFR rs12718945 1.18(0.83-1.66) 0.82(0.46-1.47) 1.12(0.77-1.64) 0.81(0.42-1.57)EGFR rs6593207 1.15(0.82-1.61) 1.46(0.97-2.19) 1.33(0.91-1.94) 1.01(0.50-2.01)EGFR rs2072454 1.21(0.85-1.72) 0.87(0.51-1.49) 1.16(0.79-1.70) 0.77(0.42-1.40)EGFR rs11536635 1.17(0.81-1.67) 0.85(0.51-1.42) 1.20(0.81-1.78) 0.72(0.41-1.29)EGFR rs11977388 1.42(1.01-2.01) 0.69(0.37-1.29) 1.44(0.99-2.11) 0.59(0.29-1.18)EGFR rs10228436 1.47(1.03-2.11) 0.88(0.52-1.48) 1.48(1.00-2.20) 0.74(0.41-1.32)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model.Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

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ABCB1 rs1045642 0.98(0.70-1.39) 0.69(0.39-1.22) 0.94(0.64-1.39) 0.72(0.39-1.34)ABCB1 rs7787082 1.19(0.81-1.75) 1.50(0.94-2.39) 1.11(0.73-1.70) 1.36(0.81-2.28)ABCB1 rs2091766 1.15(0.82-1.61) 1.46(0.97-2.19) 0.93(0.63-1.38) 0.90(0.51-1.59)ABCB1 rs1128503 0.88(0.61-1.26) 0.77(0.48-1.25) 0.85(0.57-1.27) 0.84(0.49-1.43)ABCB1 rs1922241 0.93(0.66-1.33) 0.74(0.44-1.25) 0.99(0.67-1.46) 0.83(0.46-1.49)ABCB1 rs868755 0.80(0.56-1.14) 0.95(0.56-1.59) 0.78(0.53-1.16) 1.04(0.59-1.84)ABCB1 rs2520464 0.86(0.60-1.23) 0.76(0.47-1.23) 0.82(0.55-1.23) 0.80(0.47-1.37)ABCB1 rs1202184 1.01(0.71-1.44) 0.74(0.44-1.25) 1.00(0.68-1.47) 0.80(0.45-1.43)ABCB1 rs12535512 0.89(0.61-1.29) 0.90(0.56-1.46) 1.01(0.67-1.53) 0.98(0.58-1.67)ABCB1 rs12720464 1.24(0.88-1.74) 1.38(0.65-2.91) 1.13(0.78-1.65) 1.14(0.51-2.58)ABCB1 rs1978095 1.31(0.94-1.85) 1.34(0.64-2.81) 1.22(0.83-1.77) 1.14(0.51-2.56)CDK6 rs3757823 1.13(0.76-1.66) 1.41(0.90-2.22) 0.98(0.64-1.50) 1.39(0.85-2.28)Q129R rs662 1.14(0.80-1.61) 0.65(0.36-1.17) 1.10(0.75-1.63) 0.65(0.34-1.23)L55M rs854560 0.86(0.52-1.43) 1.69(0.11-27.08) 0.86(0.48-1.53) 2.04(0.12-35.3)FGFR2 rs17157903 1.03(0.73-1.46) 1.62(0.84-3.12) 1.09(0.74-1.60) 2.03(0.96-4.29)MET rs2237710 1.15(0.82-1.61) 1.46(0.97-2.19) 1.16(0.78-1.72) 1.03(0.61-1.76)MET rs2299437 0.92(0.65-1.30) 0.87(0.51-1.50) 1.08(0.73-1.59) 1.05(0.59-1.89)MET rs10248537 0.92(0.65-1.30) 0.91(0.53-1.55) 1.08(0.73-1.59) 1.10(0.62-1.97)MET rs38855 1.26(0.88-1.82) 1.23(0.76-1.98) 1.38(0.92-2.08) 1.29(0.76-2.18)MET rs38858 1.30(0.90-1.87) 1.25(0.78-2.02) 1.39(0.93-2.09) 1.30(0.77-2.19)MET rs13223756 0.94(0.66-1.34) 0.90(0.50-1.64) 1.02(0.69-1.51) 0.95(0.50-1.79)MET rs2299440 0.94(0.66-1.34) 0.90(0.50-1.64) 1.02(0.69-1.51) 0.95(0.50-1.79)MET rs183642 1.15(0.82-1.61) 1.46(0.97-2.19) 1.10(0.72-1.69) 0.62(0.37-1.04)MET rs41736 1.17(0.79-1.72) 0.72(0.45-1.14) 1.13(0.73-1.73) 0.63(0.38-1.05)MET rs41739 1.19(0.81-1.75) 0.71(0.45-1.13) 1.15(0.75-1.77) 0.62(0.37-1.05)TBXAS1 rs6971207 0.97(0.69-1.36) 0.54(0.28-1.04) 0.93(0.63-1.35) 0.60(0.30-1.19)FGFR1 rs2304000 1.04(0.73-1.46) 1.00(0.58-1.73) 1.01(0.69-1.49) 1.04(0.58-1.87)FGFR1 rs4647907 1.05(0.74-1.48) 1.05(0.61-1.81) 1.02(0.69-1.51) 1.09(0.61-1.96)FGFR1 rs2956724 1.13(0.81-1.59) 0.80(0.40-1.61) 1.00(0.69-1.46) 0.65(0.30-1.40)FGFR1 rs2978073 1.11(0.79-1.55) 0.79(0.39-1.59) 0.99(0.68-1.44) 0.67(0.31-1.45)FGFR1 rs6983315 0.90(0.64-1.28) 1.02(0.61-1.73) 0.97(0.66-1.43) 1.22(0.68-2.18)FGFR1 rs6987534 0.93(0.66-1.31) 1.05(0.62-1.77) 1.01(0.69-1.49) 1.26(0.70-2.28)NBS1 rs9995 1.15(0.82-1.61) 1.46(0.97-2.19) 1.10(0.74-1.66) 1.02(0.61-1.70)8q24 rs13281615 0.61(0.43-0.88) 0.80(0.50-1.29) 0.71(0.48-1.06) 0.80(0.48-1.35)MYC rs3891248 0.92(0.63-1.35) 1.51(0.95-2.40) 0.97(0.64-1.47) 1.39(0.83-2.33)CDKN2A rs3731239 0.81(0.55-1.19) 0.26(0.06-1.19) 0.85(0.55-1.29) 0.26(0.06-1.21)MCS5A6 rs2182317 1.11(0.78-1.58) 1.06(0.45-2.49) 1.14(0.76-1.70) 0.98(0.41-2.35)EHMT1 rs4634736 0.86(0.08-9.49) 1.01(0.09-11.42)FLJ45983 rs1149901 0.58(0.33-1.02) 0.54(0.06-5.20) 0.41(0.22-0.80) 0.44(0.05-4.27)GATA3 rs570613 0.67(0.47-0.95) 0.53(0.31-0.93) 0.76(0.51-1.11) 0.51(0.27-0.93)GATA3 rs422628 0.73(0.43-1.23) 1.65(0.10-26.53) 0.67(0.38-1.20) 1.85(0.11-31.4)FGFR2 rs11200014 1.18(0.84-1.66) 0.94(0.49-1.79) 1.30(0.89-1.90) 0.87(0.42-1.80)FGFR2 rs2981579 1.09(0.75-1.58) 1.29(0.81-2.07) 1.12(0.74-1.69) 1.36(0.80-2.31)FGFR2 rs1078806 1.22(0.86-1.71) 0.96(0.50-1.83) 1.34(0.91-1.96) 0.89(0.43-1.84)FGFR2 rs1219648 1.15(0.82-1.61) 1.46(0.97-2.19) 1.03(0.69-1.54) 1.28(0.74-2.23)FGFR2 rs2420946 1.22(0.85-1.74) 1.26(0.77-2.06) 1.14(0.77-1.69) 1.25(0.73-2.17)FGFR2 rs2981582 1.31(0.92-1.85) 1.29(0.75-2.22) 1.39(0.94-2.06) 1.34(0.73-2.44)FGFR2 rs10510126 1.00(0.57-1.76) 1.20(0.64-2.26)LSP1 rs661348 1.26(0.88-1.81) 1.00(0.60-1.65) 1.24(0.83-1.85) 0.79(0.45-1.40)LSP1 rs3817198 0.98(0.67-1.43) 1.33(0.49-3.65) 0.95(0.63-1.44) 1.05(0.36-3.04)H19 rs2107425 0.89(0.61-1.31) 0.67(0.41-1.08) 0.87(0.57-1.32) 0.70(0.41-1.19)CCND1 rs3212891 1.15(0.82-1.61) 1.46(0.97-2.19) 0.94(0.62-1.43) 0.64(0.12-3.39)CCND1 rs678653 0.92(0.62-1.37) 1.01(0.24-4.27) 0.93(0.60-1.43) 1.00(0.23-4.34)NUMA1 rs3750913 0.99(0.60-1.63) 1.13(0.66-1.94)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

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PGR rs500760 0.92(0.64-1.31) 1.48(0.53-4.16) 0.90(0.61-1.34) 1.22(0.38-3.87)PGR rs511298 0.96(0.67-1.38) 1.48(0.49-4.47) 0.93(0.62-1.38) 1.08(0.31-3.85)PGR rs1042839 1.71(0.11-27.5) 1.23(0.08-19.92)PGR rs1042838 3.44(0.31-38.2) 2.32(0.21-26.09)PGR rs660149 0.86(0.32-2.31) 0.81(0.27-2.40)PGR rs2020876 0.64(0.17-2.43) 0.58(0.11-2.97)PGR rs7116336 1.10(0.77-1.57) 1.46(0.59-3.61) 1.09(0.74-1.61) 1.34(0.50-3.60)PGR rs11571171 1.10(0.77-1.57) 2.22(0.59-8.39) 1.12(0.75-1.66) 1.72(0.37-7.94)PGR rs566351 1.21(0.84-1.73) 1.22(0.43-3.49) 1.23(0.83-1.82) 1.13(0.33-3.91)PGR rs506487 0.86(0.08-9.49) 0.97(0.08-11.30)PGR rs518162 1.58(0.66-3.77) 1.63(0.64-4.14)MMP8 rs1892886 0.99(0.62-1.59) 0.68(0.13-3.54) 0.97(0.57-1.63) 0.51(0.09-2.77)CDKN1B rs34330 0.97(0.66-1.40) 1.22(0.78-1.92) 0.86(0.57-1.30) 1.06(0.65-1.73)IGF1 rs2946834 0.86(0.59-1.25) 0.72(0.45-1.14) 0.83(0.54-1.25) 0.69(0.41-1.14)IGF1 rs5742714 0.86(0.59-1.25) 1.18(0.51-2.72) 0.93(0.62-1.41) 1.11(0.44-2.79)IGF1 rs6214 0.90(0.61-1.33) 0.72(0.46-1.14) 1.02(0.66-1.56) 0.69(0.42-1.16)IGF1 rs1520220 1.15(0.82-1.61) 1.46(0.97-2.19) 0.84(0.56-1.26) 0.72(0.43-1.20)IGF1 rs10745940 0.87(0.60-1.25) 0.75(0.47-1.19) 0.83(0.55-1.24) 0.72(0.43-1.20)IGF1 rs5742694 0.89(0.61-1.30) 1.19(0.52-2.75) 0.95(0.63-1.45) 1.12(0.44-2.81)IGF1 rs978458 0.91(0.63-1.31) 0.75(0.47-1.19) 0.85(0.57-1.27) 0.71(0.42-1.18)IGF1 rs5742667 0.92(0.64-1.33) 0.75(0.47-1.20) 0.89(0.59-1.34) 0.70(0.42-1.17)IGF1 rs2373721 0.85(0.58-1.24) 1.27(0.55-2.97) 0.91(0.60-1.38) 1.17(0.46-2.98)IGF1 rs7136446 0.85(0.58-1.24) 1.27(0.55-2.97) 0.91(0.60-1.38) 1.17(0.46-2.98)IGF1 rs9989002 1.15(0.82-1.61) 1.46(0.97-2.19) 0.79(0.52-1.22) 1.55(0.57-4.19)IGF1 rs5742632 0.92(0.64-1.32) 0.68(0.42-1.10) 0.87(0.58-1.30) 0.66(0.39-1.12)IGF1 rs2195240 0.91(0.63-1.31) 0.69(0.43-1.12) 0.87(0.58-1.30) 0.69(0.41-1.16)IGF1 rs5742629 0.91(0.64-1.31) 0.70(0.44-1.13) 0.87(0.58-1.30) 0.68(0.40-1.14)IGF1 rs7956547 0.77(0.52-1.15) 0.97(0.35-2.71) 0.85(0.56-1.31) 0.98(0.32-3.03)IGF1 rs4764698 0.86(0.61-1.22) 0.90(0.49-1.64) 0.85(0.58-1.24) 0.72(0.36-1.44)IGF1 rs10778176 0.92(0.64-1.33) 0.68(0.43-1.09) 0.88(0.59-1.31) 0.65(0.39-1.10)IGF1 rs2162679 0.90(0.64-1.28) 0.87(0.51-1.48) 0.82(0.56-1.22) 0.68(0.37-1.23)IGF1 rs35765 1.30(0.72-2.35) 1.11(0.58-2.15)IGF1 rs7965399 0.90(0.64-1.27) 1.08(0.58-2.02) 0.93(0.64-1.35) 0.79(0.38-1.64)IGF1 rs855211 0.99(0.71-1.40) 0.94(0.53-1.69) 0.97(0.66-1.41) 0.69(0.35-1.35)BRCA2 rs144848 0.65(0.46-0.93) 1.69(0.86-3.30) 0.64(0.43-0.95) 2.19(1.02-4.72)BRCA2 rs4942485 0.67(0.29-1.56) 0.61(0.25-1.51)IRS2 rs9515118 1.15(0.82-1.61) 1.46(0.97-2.19) 1.03(0.70-1.53) 1.10(0.58-2.10)IRS2 rs4773082 0.96(0.68-1.34) 0.83(0.41-1.68) 0.95(0.65-1.38) 0.92(0.43-2.00)IRS2 rs2289046 1.21(0.82-1.78) 1.12(0.70-1.81) 1.10(0.72-1.67) 1.01(0.60-1.70)IRS2 rs754204 0.96(0.69-1.36) 1.31(0.71-2.39) 0.94(0.65-1.38) 1.52(0.79-2.95)IRS2 rs7987237 0.88(0.62-1.25) 0.71(0.34-1.48) 0.88(0.59-1.30) 0.82(0.38-1.77)IRS2 rs12584136 1.29(0.74-2.25) 1.35(0.74-2.46)IRS2 rs9559648 0.90(0.63-1.27) 1.06(0.45-2.52) 0.80(0.54-1.18) 0.99(0.38-2.58)IRS2 rs9559654 1.01(0.71-1.44) 1.26(0.50-3.20) 0.90(0.60-1.33) 1.02(0.36-2.88)IRS2 rs7997595 0.86(0.61-1.22) 0.53(0.26-1.10) 0.85(0.58-1.26) 0.69(0.33-1.47)IRS2 rs7981705 1.28(0.67-2.46) 1.60(0.80-3.19)IRS2 rs4773092 1.42(0.96-2.10) 1.14(0.71-1.82) 1.41(0.91-2.17) 1.14(0.68-1.92)ESR2 rs1255998 1.15(0.82-1.61) 1.46(0.97-2.19) 1.40(0.92-2.11) 1.03(0.59-1.78)ESR2 rs8018687 0.98(0.62-1.54) 1.13(0.19-6.85) 0.88(0.53-1.47) 0.97(0.16-5.97)ESR2 rs928554 1.23(0.87-1.75) 0.94(0.55-1.60) 1.35(0.91-1.99) 1.10(0.61-1.99)ESR2 rs1152579 1.26(0.89-1.80) 0.95(0.56-1.62) 1.38(0.93-2.04) 1.11(0.61-2.02)ESR2 rs1256049 1.15(0.82-1.62) 0.94(0.47-1.87) 1.30(0.89-1.89) 0.87(0.39-1.94)ESR2 rs1256030 1.25(0.87-1.78) 0.93(0.55-1.57) 1.36(0.91-2.02) 1.11(0.62-1.99)ESR2 rs1271572 1.24(0.87-1.77) 0.93(0.55-1.57) 1.35(0.91-2.02) 1.07(0.59-1.94)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

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XRCC3 rs861539 1.15(0.82-1.61) 1.00(0.50-2.00)XRCC3 rs1799796 0.78(0.55-1.10) 0.66(0.37-1.17) 0.69(0.47-1.01) 0.60(0.32-1.13)XRCC3 rs1799794 0.85(0.58-1.24) 0.66(0.42-1.05) 0.76(0.49-1.16) 0.64(0.38-1.06)AKT1 rs2494744 1.04(0.73-1.48) 1.19(0.72-1.97) 0.88(0.60-1.29) 1.03(0.58-1.82)AKT1 rs2498787 0.89(0.63-1.27) 1.15(0.70-1.88) 0.75(0.51-1.11) 1.03(0.59-1.80)CYP20 rs4646 0.85(0.60-1.20) 0.68(0.36-1.27) 0.82(0.56-1.21) 0.56(0.27-1.16)CYP19 rs10046 0.91(0.62-1.33) 0.85(0.53-1.37) 0.83(0.55-1.25) 0.83(0.49-1.40)CYP21 rs727479 1.15(0.82-1.61) 1.46(0.97-2.19) 0.81(0.56-1.19) 0.55(0.28-1.07)MAP2K1 rs7174378 0.84(0.57-1.22) 0.83(0.52-1.31) 0.92(0.60-1.39) 0.90(0.54-1.51)MAP2K1 rs7181936 0.88(0.62-1.25) 0.96(0.58-1.59) 0.85(0.58-1.26) 0.96(0.55-1.65)MAP2K1 rs28620576 0.89(0.63-1.25) 1.17(0.65-2.12) 0.99(0.67-1.44) 1.23(0.65-2.33)MAP2K1 rs8039880 0.80(0.56-1.15) 0.87(0.54-1.39) 0.91(0.61-1.36) 1.02(0.60-1.71)CYP1A1 rs1048943 1.03(0.73-1.47) 1.31(0.60-2.86) 1.13(0.76-1.66) 1.23(0.52-2.90)IGF1R rs4966007 1.08(0.76-1.54) 0.86(0.51-1.42) 1.32(0.89-1.95) 1.03(0.58-1.83)IGF1R rs8028620 1.15(0.82-1.61) 1.46(0.97-2.19) 1.41(0.91-2.17) 1.21(0.72-2.05)IGF1R rs4966009 1.09(0.77-1.56) 0.91(0.55-1.52) 1.36(0.92-2.01) 1.09(0.61-1.95)IGF1R rs8027457 1.17(0.79-1.72) 1.00(0.63-1.58) 1.47(0.95-2.26) 1.21(0.72-2.05)IGF1R rs4966012 1.16(0.83-1.63) 0.94(0.50-1.77) 1.24(0.85-1.81) 0.98(0.49-1.96)IGF1R rs1574213 1.08(0.76-1.52) 1.63(0.67-3.93) 1.11(0.75-1.62) 1.77(0.68-4.58)IGF1R rs11630479 1.17(0.83-1.64) 0.98(0.52-1.84) 1.26(0.87-1.84) 1.05(0.52-2.10)IGF1R rs4966013 1.15(0.78-1.70) 1.22(0.77-1.93) 1.22(0.79-1.87) 1.13(0.68-1.87)IGF1R rs4966015 1.15(0.82-1.61) 1.46(0.97-2.19) 0.93(0.64-1.35) 0.77(0.29-2.08)IGF1R rs8032477 1.21(0.82-1.79) 0.68(0.41-1.12) 1.17(0.76-1.80) 0.57(0.33-0.99)IGF1R rs11634241 0.93(0.66-1.31) 0.93(0.52-1.65) 0.92(0.63-1.35) 0.81(0.43-1.54)IGF1R rs932071 0.96(0.68-1.36) 0.93(0.43-1.99) 1.00(0.68-1.47) 0.75(0.33-1.74)IGF1R rs875686 0.93(0.66-1.31) 0.79(0.38-1.62) 0.97(0.66-1.42) 0.75(0.34-1.68)IGF1R rs1567811 1.15(0.81-1.64) 0.74(0.43-1.26) 1.06(0.72-1.57) 0.75(0.42-1.35)IGF1R rs11632952 0.96(0.68-1.36) 0.96(0.46-2.02) 1.04(0.71-1.54) 0.75(0.34-1.68)IGF1R rs4966024 1.15(0.82-1.61) 1.46(0.97-2.19) 1.10(0.71-1.70) 0.76(0.44-1.30)IGF1R rs8041224 1.15(0.80-1.65) 0.66(0.39-1.12) 1.07(0.72-1.59) 0.63(0.35-1.12)IGF1R rs7175052 1.23(0.86-1.75) 0.59(0.34-1.02) 1.12(0.75-1.65) 0.54(0.30-0.98)IGF1R rs2137680 1.40(0.94-2.07) 0.74(0.45-1.22) 1.29(0.84-1.99) 0.62(0.36-1.07)IGF1R rs12439557 1.06(0.75-1.49) 0.62(0.33-1.20) 1.13(0.77-1.65) 0.54(0.26-1.12)IGF1R rs4966028 0.88(0.59-1.30) 1.51(0.60-3.80) 0.88(0.57-1.35) 2.02(0.74-5.50)IGF1R rs907806 0.82(0.56-1.22) 2.14(0.78-5.85) 0.84(0.55-1.29) 3.11(0.99-9.75)IGF1R rs8041953 1.15(0.82-1.61) 1.46(0.97-2.19) 0.84(0.55-1.29) 1.83(0.61-5.46)IGF1R rs2670501 0.79(0.55-1.13) 1.06(0.67-1.70) 0.72(0.48-1.07) 0.95(0.56-1.60)IGF1R rs4246340 0.87(0.59-1.26) 1.12(0.70-1.79) 0.87(0.57-1.32) 1.17(0.70-1.94)IGF1R rs2684777 0.78(0.55-1.13) 1.01(0.62-1.64) 0.83(0.56-1.24) 1.16(0.68-1.97)IGF1R rs8030950 1.22(0.87-1.72) 0.76(0.35-1.63) 1.14(0.78-1.67) 0.68(0.29-1.61)IGF1R rs12594847 1.19(0.83-1.69) 1.00(0.59-1.68) 1.09(0.73-1.61) 0.99(0.57-1.74)IGF1R rs2684781 1.32(0.92-1.89) 1.12(0.68-1.85) 1.22(0.82-1.81) 1.05(0.61-1.80)IGF1R rs1521481 1.15(0.82-1.61) 1.46(0.97-2.19) 1.15(0.79-1.68) 0.36(0.13-0.98)IGF1R rs4966035 0.78(0.53-1.15) 1.02(0.65-1.60) 0.65(0.42-0.98) 0.84(0.51-1.39)IGF1R rs4966036 0.80(0.56-1.14) 0.92(0.56-1.52) 0.87(0.58-1.28) 1.12(0.65-1.93)IGF1R rs7165875 0.82(0.56-1.20) 1.03(0.66-1.62) 0.69(0.45-1.05) 0.83(0.50-1.38)IGF1R rs3743259 0.78(0.53-1.14) 1.03(0.66-1.63) 0.66(0.43-1.00) 0.84(0.50-1.40)IGF1R rs3743260 1.06(0.72-1.56) 1.27(0.50-3.22) 1.10(0.72-1.69) 1.31(0.49-3.46)IGF1R rs2684810 1.28(0.91-1.80) 0.68(0.34-1.36) 1.10(0.76-1.60) 0.66(0.31-1.40)IGF1R rs4966039 1.15(0.82-1.61) 1.46(0.97-2.19) 0.86(0.58-1.28) 0.85(0.31-2.35)IGF1R rs2684805 1.10(0.76-1.59) 1.14(0.71-1.82) 1.18(0.79-1.78) 1.14(0.67-1.93)IGF1R rs2684803 0.86(0.61-1.22) 0.79(0.46-1.35) 0.91(0.62-1.34) 0.69(0.37-1.26)IGF1R rs1546713 0.87(0.61-1.23) 0.79(0.46-1.36) 0.92(0.62-1.35) 0.69(0.37-1.26)IGF1R rs7166558 0.87(0.62-1.24) 0.79(0.46-1.36) 0.93(0.64-1.37) 0.69(0.37-1.26)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

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IGF1R rs2229765 0.83(0.58-1.18) 0.79(0.46-1.37) 0.88(0.60-1.30) 0.69(0.37-1.26)IGF1R rs11635251 1.08(0.77-1.53) 0.98(0.57-1.70) 0.97(0.66-1.42) 0.92(0.51-1.67)IGF1R rs8038056 1.15(0.82-1.61) 1.46(0.97-2.19) 1.28(0.87-1.88) 1.12(0.61-2.05)IGF1R rs12916884 1.19(0.84-1.68) 0.82(0.48-1.39) 1.09(0.74-1.61) 0.82(0.46-1.46)IGF1R rs7173377 1.24(0.87-1.75) 1.10(0.65-1.86) 1.26(0.85-1.85) 1.21(0.68-2.17)IGF1R rs7166565 1.24(0.88-1.77) 1.29(0.78-2.13) 1.27(0.86-1.87) 1.47(0.84-2.56)IGF1R rs939626 1.17(0.83-1.65) 0.70(0.35-1.37) 1.27(0.87-1.86) 0.73(0.33-1.60)IGF1R rs12437963 0.84(0.59-1.20) 0.83(0.50-1.39) 0.90(0.61-1.33) 0.83(0.47-1.46)IGF1R rs2684788 0.91(0.63-1.32) 0.77(0.48-1.24) 0.94(0.62-1.41) 0.78(0.46-1.32)IGF1R rs1815009 1.15(0.82-1.61) 1.46(0.97-2.19) 1.13(0.75-1.70) 0.79(0.47-1.34)A2BP1 rs7203563 0.78(0.54-1.12) 0.56(0.20-1.59) 0.81(0.54-1.20) 0.84(0.27-2.59)TNRC9/LOC643714 rs8051542 1.27(0.90-1.79) 1.35(0.58-3.12) 1.22(0.83-1.78) 1.40(0.58-3.36)TNRC9/LOC643714 rs12443621 1.05(0.74-1.50) 1.33(0.80-2.20) 1.08(0.73-1.60) 1.30(0.75-2.28)TNRC9 or TOX3 rs3803662 0.78(0.55-1.11) 0.77(0.47-1.27) 0.75(0.51-1.11) 0.64(0.36-1.14)ATP1B2 rs1641512 0.98(0.69-1.41) 1.05(0.66-1.69) 1.00(0.67-1.49) 1.26(0.74-2.13)TP53 rs9894946 1.35(0.74-2.48) 1.31(0.69-2.51)TP53 rs1614984 1.01(0.72-1.43) 0.88(0.51-1.51) 1.10(0.75-1.61) 0.99(0.53-1.86)TP53 rs1042522 0.99(0.69-1.42) 0.94(0.57-1.57) 0.98(0.66-1.45) 1.02(0.57-1.79)WDR79 rs2287499 1.00(0.71-1.40) 1.32(0.67-2.63) 1.08(0.74-1.57) 1.37(0.62-3.02)WDR79 rs17885803 0.94(0.61-1.46) 0.85(0.08-9.38) 0.82(0.50-1.34) 0.85(0.08-9.65)WDR79 rs2287498 1.00(0.71-1.40) 1.33(0.67-2.65) 1.07(0.73-1.56) 1.37(0.62-3.03)HER2 rs1565923 1.24(0.86-1.79) 1.46(0.89-2.39) 1.10(0.74-1.66) 1.19(0.69-2.06)ERBB rs1810132 1.25(0.87-1.81) 1.47(0.90-2.41) 1.12(0.75-1.68) 1.20(0.69-2.07)HER2 rs3809717 0.93(0.66-1.32) 1.49(0.83-2.69) 0.84(0.57-1.24) 1.38(0.73-2.60)ITGB3 rs3809865 0.80(0.56-1.14) 1.00(0.44-2.25) 0.82(0.55-1.21) 0.75(0.29-1.96)ITGA3 rs1062484 0.34(0.04-2.92) 0.31(0.03-2.88)AXIN2 rs7210356 1.09(0.74-1.60) 0.72(0.25-2.08) 1.14(0.75-1.75) 0.53(0.16-1.79)AXIN2 rs4791171 0.85(0.60-1.20) 0.55(0.31-0.97) 0.80(0.54-1.18) 0.47(0.25-0.88)AXIN2 rs11079571 1.25(0.88-1.76) 1.41(0.78-2.55) 1.26(0.86-1.84) 1.35(0.67-2.72)AXIN2 rs3923087 0.84(0.59-1.18) 0.61(0.34-1.09) 0.82(0.56-1.20) 0.54(0.28-1.04)AXIN2 rs3923086 0.60(0.41-0.88) 0.44(0.12-1.64) 0.65(0.42-1.00) 0.33(0.07-1.58)GPX4 rs4807542 1.15(0.82-1.61) 1.46(0.97-2.19) 1.26(0.86-1.86) 0.32(0.09-1.13)MAP2K2 rs350916 1.27(0.90-1.80) 0.98(0.57-1.68) 1.20(0.81-1.76) 0.88(0.49-1.58)MAP2K2 rs350913 1.38(0.98-1.96) 0.87(0.51-1.51) 1.34(0.91-1.99) 0.79(0.44-1.42)MAP2K2 rs7258366 1.45(1.03-2.04) 0.95(0.52-1.74) 1.43(0.98-2.10) 0.80(0.41-1.57)MAP2K2 rs350894 1.46(1.01-2.10) 1.13(0.67-1.91) 1.46(0.98-2.18) 1.01(0.58-1.78)MAP2K2 rs12459484 1.45(1.02-2.06) 0.96(0.57-1.63) 1.45(0.98-2.15) 0.98(0.55-1.75)ICAM5 rs1056538 1.06(0.75-1.50) 1.25(0.71-2.19) 0.98(0.67-1.44) 0.95(0.51-1.76)CCNE1 rs997669 1.15(0.82-1.61) 1.46(0.97-2.19) 1.21(0.74-1.98) 1.17(0.19-7.25)XRCC1 rs25487 1.13(0.80-1.59) 2.09(1.05-4.17) 1.18(0.81-1.73) 1.81(0.83-3.95)DNMT3B rs406193PTGIS rs6095541 1.28(0.83-1.96) 3.59(0.32-39.90) 1.40(0.88-2.24) 2.27(0.20-25.6)PTGIS rs6095543 1.17(0.81-1.69) 2.41(1.03-5.62) 1.17(0.78-1.75) 2.58(1.01-6.59)PTGIS rs693649 0.95(0.67-1.36) 0.83(0.50-1.36) 0.93(0.63-1.37) 0.85(0.48-1.50)AURKA rs8173 1.07(0.75-1.51) 1.48(0.85-2.57) 1.26(0.85-1.85) 1.62(0.88-2.96)AURKA rs10485805 0.98(0.69-1.37) 1.37(0.62-3.02) 1.17(0.80-1.70) 1.22(0.50-3.00)AURKA rs6024840 1.15(0.82-1.61) 1.46(0.97-2.19) 1.53(1.04-2.24) 0.92(0.48-1.75)AURKA rs911160 1.26(0.89-1.78) 0.97(0.55-1.71) 1.50(1.02-2.20) 0.95(0.51-1.78)AURKA rs2298016 1.18(0.83-1.67) 1.05(0.61-1.79) 1.38(0.94-2.04) 1.03(0.57-1.86)AURKA rs2273535 1.19(0.84-1.69) 1.05(0.61-1.79) 1.40(0.95-2.07) 1.03(0.57-1.88)COMT rs4680 0.67(0.47-0.94) 1.11(0.58-2.10) 0.65(0.44-0.94) 1.22(0.60-2.49)CHEK2 rs9608698 0.81(0.57-1.14) 1.62(0.73-3.59) 0.73(0.50-1.07) 1.71(0.75-3.91)PHKA1 rs3012642 0.98(0.68-1.43) 1.03(0.37-2.89) 　 0.90(0.59-1.36) 1.12(0.39-3.19)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition...

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　　 HER2 (additive model)Hetero Minor Hetero Minor


MTHFR rs1801131 1.08(0.70-1.67) 1.01(0.36-2.85) 1.09(0.68-1.74) 1.28(0.43-3.82)RIZ1 or PRDM2 rs2235515 1.18(0.74-1.88) 1.20(0.67-2.16) 1.01(0.61-1.67) 1.06(0.56-1.98)HSD11B1 rs4393158 1.03(0.67-1.59) 1.05(0.55-2.01) 1.06(0.66-1.69) 1.11(0.56-2.22)HSD11B1 rs2235543 1.00(0.65-1.56) 0.89(0.48-1.65) 1.06(0.66-1.71) 0.85(0.44-1.64)HSD11B1 rs11807619 0.77(0.49-1.22) 0.41(0.09-1.84) 0.85(0.52-1.38) 0.48(0.10-2.27)HSD11B1 rs932335 0.71(0.44-1.14) 0.26(0.03-2.01) 0.74(0.45-1.23) 0.26(0.03-2.16)2p(19150424) rs4666451 1.66(0.83-3.35) 1.73(0.82-3.63)CYP1B1 rs1800440 3.20(0.45-22.9) 2.52(0.35-18.2)CYP1B1 rs1056836 1.49(0.93-2.39) 1.74(0.16-19.40) 1.10(0.65-1.85) 1.22(0.10-14.40)ITGA6 rs17664 1.04(0.64-1.68) 0.31(0.04-2.47) 1.07(0.64-1.79) 0.48(0.06-4.10)ITGAv rs11902171 0.74(0.40-1.37) 1.52(0.14-16.96) 0.69(0.36-1.34) 2.05(0.12-34.50)BARD1 rs6759222 1.17(0.66-2.07) 2.18(0.36-13.22) 1.30(0.71-2.38) 0.76(0.08-7.53)BARD1 rs4673896 0.85(0.55-1.33) 1.01(0.56-1.82) 0.73(0.45-1.18) 0.82(0.43-1.55)BARD1 rs6717301 0.98(0.61-1.57) 0.84(0.47-1.50) 1.24(0.74-2.08) 1.23(0.66-2.30)BARD1 rs2229571 1.03(0.67-1.60) 0.95(0.50-1.82) 0.88(0.55-1.42) 0.76(0.38-1.54)BARD1 rs3768704 1.00(0.63-1.58) 0.71(0.39-1.30) 1.23(0.75-2.03) 0.98(0.52-1.86)BARD1 rs7591615 1.09(0.55-2.18) 1.23(0.59-2.54)BARD1 rs6435862 1.44(0.93-2.23) 0.88(0.18-4.21) 1.26(0.78-2.02) 0.36(0.04-2.99)2q35 rs13387042 1.06(0.63-1.79) 0.80(0.09-7.22) 1.29(0.74-2.24) 1.04(0.10-10.72)FGFR2 rs12505080 0.96(0.60-1.52) 0.93(0.52-1.65) 1.09(0.66-1.79) 1.01(0.54-1.86)FGFR2 rs7696175 1.09(0.69-1.74) 0.54(0.06-4.50) 1.26(0.76-2.09) 0.52(0.05-5.06)KIT rs2237038 1.08(0.68-1.69) 0.71(0.36-1.37) 0.95(0.59-1.54) 0.59(0.28-1.24)KIT rs981959 1.06(0.67-1.66) 0.70(0.36-1.36) 0.94(0.58-1.52) 0.59(0.28-1.22)KIT rs2237034 1.18(0.77-1.80) 0.87(0.34-2.22) 1.16(0.73-1.83) 0.93(0.33-2.66)KIT rs2237032 1.06(0.69-1.61) 0.90(0.41-1.98) 0.98(0.62-1.54) 0.87(0.37-2.07)KIT rs2237023 1.11(0.72-1.72) 1.15(0.59-2.26) 1.10(0.69-1.75) 0.91(0.43-1.92)KIT rs6810872 1.08(0.70-1.67) 1.05(0.53-2.09) 1.07(0.67-1.70) 0.82(0.38-1.77)KIT rs3134884 0.93(0.60-1.43) 0.76(0.25-2.35) 0.91(0.57-1.45) 0.72(0.23-2.26)KIT rs3111800 0.78(0.49-1.26) 0.91(0.51-1.62) 0.74(0.45-1.24) 0.87(0.47-1.63)KIT rs2237018 0.95(0.62-1.46) 1.08(0.50-2.34) 0.88(0.55-1.40) 1.13(0.48-2.63)KIT rs6843170 0.89(0.58-1.37) 0.97(0.44-2.16) 0.81(0.51-1.31) 1.02(0.42-2.45)KDR rs17709898 1.10(0.72-1.69) 1.48(0.69-3.17) 1.17(0.73-1.86) 1.48(0.64-3.41)KDR rs12505758 0.86(0.56-1.33) 0.49(0.16-1.44) 0.72(0.45-1.16) 0.32(0.09-1.13)KDR rs2168945 1.10(0.72-1.70) 0.84(0.43-1.63) 1.20(0.75-1.91) 1.03(0.50-2.09)KDR rs13136007 1.23(0.77-1.95) 1.39(0.78-2.49) 1.33(0.81-2.19) 1.49(0.79-2.81)KDR rs11732292 1.11(0.72-1.71) 0.80(0.40-1.58) 1.22(0.76-1.93) 0.99(0.48-2.04)KDR rs1870377 1.40(0.88-2.23) 1.42(0.79-2.55) 1.49(0.90-2.46) 1.56(0.83-2.96)KDR rs7673274 0.89(0.58-1.38) 0.54(0.20-1.45) 0.71(0.44-1.13) 0.39(0.13-1.19)KDR rs11133360 1.23(0.79-1.92) 1.12(0.61-2.08) 1.05(0.65-1.70) 1.06(0.55-2.06)STE or SULT1E1 rs3775775 1.32(0.72-2.40) 4.99(0.82-30.27) 1.11(0.57-2.15) 3.43(0.54-21.87)STE or SULT1E1 rs1881668 1.80(1.14-2.86) 2.36(1.30-4.29) 1.48(0.90-2.42) 2.17(1.14-4.10)ADH1B rs1042026 0.87(0.56-1.35) 1.10(0.34-3.56) 1.00(0.62-1.62) 1.21(0.36-4.07)5p12 rs4415084 0.97(0.61-1.54) 0.69(0.38-1.24) 1.04(0.63-1.71) 0.82(0.44-1.54)MRPS30 rs10941679 1.07(0.66-1.74) 1.24(0.71-2.17) 1.00(0.59-1.68) 1.15(0.63-2.11)5p14 rs7703618 0.59(0.38-0.91) 0.65(0.32-1.33) 0.56(0.35-0.90) 0.71(0.33-1.55)5p15 rs10035564 1.13(0.70-1.84) 1.46(0.83-2.58) 1.07(0.63-1.80) 1.50(0.82-2.74)5p(45321475bp) rs981782 0.81(0.52-1.25) 0.95(0.52-1.72) 0.79(0.49-1.27) 0.88(0.47-1.67)5q(52454339bp) rs30099 0.71(0.45-1.12) 1.18(0.66-2.12) 0.70(0.43-1.13) 1.12(0.59-2.13)MAP3K1 rs889312 0.86(0.55-1.37) 0.79(0.44-1.41) 0.87(0.53-1.42) 0.68(0.36-1.27)DHFR rs1677666 1.13(0.40-3.22) 1.23(0.41-3.67)APC rs11954856 1.02(0.66-1.59) 0.73(0.20-2.61) 0.98(0.61-1.57) 0.81(0.20-3.26)APC rs11241183 0.97(0.63-1.50) 1.30(0.66-2.58) 1.02(0.64-1.62) 1.29(0.62-2.71)APC rs2439591 1.06(0.69-1.64) 0.68(0.19-2.44) 1.03(0.65-1.64) 0.77(0.20-3.05)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

Table 9-1. Association of 384 SNPs with HER2-Overexpressing breast cancer risk

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Table 9-2. Association of 384 SNPs with HER2-Overexpressing breast cancer risk　　 HER2 (additive model)


APC rs2431512 0.90(0.58-1.38) 1.35(0.70-2.59) 0.99(0.62-1.58) 1.32(0.65-2.69)APC rs2431238 1.31(0.78-2.20) 1.23(0.70-2.16)APC rs454886 0.92(0.60-1.42) 1.27(0.65-2.48) 0.94(0.59-1.49) 1.46(0.70-3.03)APC rs501250 1.11(0.65-1.92) 0.95(0.52-1.73)APC rs2229992 0.94(0.61-1.45) 1.45(0.73-2.88) 0.96(0.60-1.54) 1.49(0.70-3.16)APC rs41116 0.88(0.57-1.36) 1.32(0.64-2.75) 0.89(0.56-1.41) 1.42(0.64-3.16)APC rs448475 0.87(0.56-1.34) 1.31(0.63-2.72) 0.87(0.54-1.38) 1.40(0.63-3.12)CDKN1A rs3176336 1.09(0.71-1.66) 0.57(0.23-1.42) 1.04(0.65-1.64) 0.69(0.27-1.78)CDKN1A rs1801270 0.91(0.56-1.47) 0.96(0.54-1.70) 0.85(0.51-1.42) 0.87(0.47-1.61)CCND3 rs2479717 1.19(0.69-2.05) 1.28(0.72-2.28)LSP1 rs381798 0.87(0.55-1.35) 0.81(0.45-1.48) 0.86(0.53-1.39) 0.80(0.42-1.53)ECHDC1 rs2180341 1.42(0.94-2.17) 1.21(0.54-2.71) 1.55(0.98-2.45) 1.49(0.63-3.51)ECHDC1 rs6569479 1.42(0.93-2.16) 1.20(0.54-2.70) 1.54(0.98-2.43) 1.48(0.63-3.48)ECHDC1 rs6569480 1.43(0.94-2.18) 1.21(0.54-2.71) 1.56(0.99-2.47) 1.49(0.63-3.50)ECHDC1 rs7776136 1.43(0.94-2.18) 1.23(0.55-2.75) 1.52(0.96-2.41) 1.48(0.63-3.49)ESR1 rs851984 1.03(0.62-1.71) 0.95(0.26-3.54) 1.06(0.62-1.80) 0.44(0.09-2.09)ESR1 rs851982 1.00(0.60-1.66) 0.95(0.26-3.51) 1.01(0.59-1.72) 0.43(0.09-2.07)ESR1 rs2881766 1.66(1.04-2.65) 1.38(0.74-2.56) 1.80(1.08-2.98) 1.73(0.90-3.34)ESR1 rs2077647 1.30(0.84-2.02) 1.41(0.77-2.59) 1.52(0.94-2.45) 1.81(0.94-3.47)ESR1 rs9322331 1.06(0.38-2.97) 0.97(0.34-2.80)ESR1 rs712221 1.26(0.79-2.01) 1.23(0.68-2.21) 1.41(0.84-2.37) 1.40(0.75-2.65)ESR1 rs1801132 1.05(0.64-1.73) 1.12(0.63-1.99) 1.00(0.58-1.71) 1.20(0.65-2.23)ESR1 rs3020314 1.17(0.76-1.80) 0.27(0.04-2.11) 1.37(0.86-2.18) 0.31(0.04-2.51)ESR1 rs3020377 1.20(0.78-1.85) 0.25(0.03-1.96) 1.39(0.87-2.21) 0.28(0.03-2.21)ESR1 rs3020390 0.95(0.62-1.46) 0.96(0.49-1.88) 1.07(0.68-1.70) 0.92(0.45-1.91)ESR1 rs3020317 0.82(0.52-1.30) 0.93(0.52-1.65) 0.85(0.51-1.40) 0.95(0.52-1.75)ESR1 rs3020394 0.98(0.64-1.51) 0.91(0.47-1.76) 1.07(0.67-1.71) 0.87(0.43-1.76)ESR1 rs3020396 0.91(0.59-1.40) 0.87(0.46-1.66) 0.97(0.61-1.55) 0.82(0.41-1.62)ESR1 rs3020401 0.93(0.60-1.43) 0.90(0.47-1.70) 0.99(0.62-1.59) 0.84(0.42-1.68)ESR1 rs1884051 0.80(0.50-1.28) 0.89(0.51-1.56) 0.73(0.44-1.22) 0.81(0.45-1.47)ESR1 rs1884054 1.07(0.70-1.63) 0.87(0.38-1.99) 1.23(0.78-1.94) 0.79(0.32-1.95)ESR1 rs3020405 1.04(0.68-1.58) 0.89(0.40-1.97) 1.21(0.77-1.91) 0.80(0.34-1.88)ESR1 rs726282 0.78(0.50-1.20) 0.67(0.36-1.27) 0.75(0.46-1.20) 0.69(0.35-1.34)ESR1 rs3020407 1.07(0.70-1.64) 1.13(0.55-2.32) 1.23(0.78-1.95) 1.06(0.49-2.31)ESR1 rs6905370 0.78(0.48-1.26) 1.45(0.85-2.50) 0.69(0.41-1.16) 1.31(0.72-2.37)ESR1 rs926778 1.17(0.75-1.82) 0.85(0.46-1.59) 1.31(0.81-2.11) 1.00(0.51-1.95)ESR1 rs3020366 1.21(0.76-1.92) 1.03(0.58-1.85) 1.19(0.72-1.95) 0.85(0.44-1.62)ESR1 rs2273206 0.94(0.61-1.44) 1.04(0.54-2.00) 0.98(0.61-1.56) 1.04(0.52-2.09)ESR1 rs750686 1.09(0.68-1.76) 1.08(0.61-1.91) 0.99(0.60-1.66) 0.88(0.47-1.65)ESR1 rs2228480 0.98(0.64-1.49) 0.55(0.16-1.93) 1.08(0.68-1.71) 0.87(0.23-3.27)ESR1 rs3798577 0.87(0.56-1.35) 0.79(0.41-1.50) 0.83(0.52-1.34) 0.96(0.48-1.93)ESR1 rs910416 0.86(0.56-1.33) 0.66(0.34-1.28) 0.85(0.53-1.36) 0.73(0.36-1.48)IGFBP3 rs2854744 0.92(0.58-1.45) 0.55(0.22-1.35) 0.91(0.56-1.48) 0.57(0.22-1.44)EGFR rs11770506 0.79(0.52-1.22) 0.56(0.26-1.21) 0.71(0.44-1.13) 0.55(0.24-1.25)EGFR rs4947974 1.01(0.66-1.55) 1.15(0.59-2.24) 0.86(0.54-1.37) 1.15(0.55-2.37)EGFR rs2110290 1.08(0.70-1.66) 1.20(0.61-2.37) 0.93(0.58-1.47) 1.20(0.57-2.53)EGFR rs12667668 1.49(0.96-2.30) 1.23(0.62-2.43) 1.59(1.00-2.53) 0.98(0.45-2.13)EGFR rs12718945 1.42(0.92-2.19) 1.31(0.67-2.55) 1.49(0.94-2.38) 1.04(0.49-2.24)EGFR rs6593207 1.63(1.07-2.49) 1.11(0.52-2.37) 1.78(1.12-2.82) 1.01(0.44-2.36)EGFR rs2072454 1.48(0.95-2.30) 1.26(0.66-2.39) 1.73(1.07-2.80) 1.17(0.59-2.34)EGFR rs11536635 1.35(0.85-2.14) 1.47(0.81-2.66) 1.58(0.96-2.60) 1.29(0.68-2.47)EGFR rs11977388 1.48(0.96-2.27) 1.10(0.55-2.20) 1.83(1.14-2.92) 0.94(0.45-1.99)EGFR rs10228436 1.49(0.95-2.36) 1.38(0.76-2.51) 1.69(1.04-2.76) 1.16(0.60-2.24)ABCB1 rs1045642 1.14(0.74-1.76) 1.10(0.58-2.10) 1.05(0.66-1.69) 0.88(0.44-1.78)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

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ABCB1 rs7787082 1.10(0.70-1.75) 0.92(0.50-1.68) 0.96(0.59-1.57) 0.86(0.45-1.65)ABCB1 rs2091766 0.87(0.57-1.34) 0.54(0.27-1.08) 1.05(0.66-1.66) 0.75(0.35-1.58)ABCB1 rs1128503 0.95(0.61-1.46) 0.50(0.26-0.99) 1.07(0.67-1.71) 0.59(0.29-1.22)ABCB1 rs1922241 0.85(0.55-1.30) 0.57(0.28-1.13) 1.03(0.65-1.62) 0.76(0.36-1.60)ABCB1 rs868755 1.09(0.70-1.71) 1.39(0.74-2.59) 1.09(0.67-1.77) 1.22(0.62-2.39)ABCB1 rs2520464 0.85(0.55-1.31) 0.43(0.22-0.86) 0.95(0.59-1.51) 0.49(0.23-1.02)ABCB1 rs1202184 0.76(0.50-1.17) 0.44(0.21-0.91) 0.78(0.49-1.24) 0.46(0.21-1.03)ABCB1 rs12535512 1.03(0.64-1.64) 1.08(0.60-1.96) 0.97(0.59-1.61) 1.02(0.54-1.91)ABCB1 rs12720464 1.43(0.94-2.19) 2.37(1.06-5.30) 1.25(0.79-1.97) 2.63(1.13-6.13)ABCB1 rs1978095 1.45(0.95-2.21) 2.47(1.14-5.38) 1.27(0.80-2.01) 2.77(1.22-6.31)CDK6 rs3757823 2.17(1.27-3.72) 2.15(1.16-3.99) 2.36(1.31-4.25) 2.65(1.35-5.20)Q129R rs662 1.11(0.72-1.71) 0.76(0.38-1.55) 1.07(0.67-1.72) 0.75(0.35-1.59)L55M rs854560 1.12(0.62-2.03) 3.23(0.20-52.03) 1.16(0.62-2.18) 2.74(0.14-53.07)FGFR2 rs17157903 0.83(0.53-1.28) 1.29(0.57-2.94) 0.87(0.54-1.40) 1.78(0.73-4.36)MET rs2237710 1.10(0.71-1.70) 0.73(0.38-1.41) 1.03(0.64-1.65) 0.71(0.36-1.41)MET rs2299437 0.92(0.60-1.40) 0.62(0.29-1.30) 0.94(0.59-1.48) 0.66(0.30-1.43)MET rs10248537 0.92(0.60-1.40) 0.62(0.29-1.30) 0.94(0.59-1.48) 0.66(0.30-1.43)MET rs38855 1.04(0.67-1.61) 0.85(0.46-1.58) 1.13(0.70-1.82) 0.88(0.46-1.68)MET rs38858 1.03(0.66-1.59) 0.91(0.50-1.66) 1.11(0.69-1.79) 0.95(0.51-1.80)MET rs13223756 1.12(0.73-1.70) 0.26(0.08-0.89) 1.19(0.75-1.87) 0.28(0.08-0.95)MET rs2299440 1.12(0.73-1.70) 0.26(0.08-0.89) 1.19(0.75-1.87) 0.28(0.08-0.95)MET rs183642 1.15(0.71-1.87) 0.92(0.52-1.61) 1.09(0.65-1.83) 0.89(0.49-1.60)MET rs41736 1.16(0.71-1.88) 0.91(0.52-1.59) 1.10(0.65-1.85) 0.88(0.49-1.58)MET rs41739 1.17(0.72-1.90) 0.90(0.51-1.58) 1.11(0.66-1.87) 0.87(0.48-1.56)TBXAS1 rs6971207 1.17(0.77-1.79) 0.81(0.38-1.72) 1.24(0.79-1.97) 0.74(0.33-1.66)FGFR1 rs2304000 1.27(0.83-1.97) 1.21(0.62-2.35) 1.28(0.80-2.04) 1.32(0.64-2.70)FGFR1 rs4647907 1.33(0.86-2.06) 1.29(0.66-2.52) 1.33(0.83-2.13) 1.40(0.68-2.88)FGFR1 rs2956724 0.90(0.59-1.38) 1.28(0.61-2.65) 0.89(0.56-1.41) 1.28(0.58-2.82)FGFR1 rs2978073 0.94(0.61-1.44) 1.30(0.62-2.70) 0.95(0.60-1.51) 1.32(0.60-2.92)FGFR1 rs6983315 0.88(0.57-1.34) 0.65(0.32-1.34) 0.74(0.46-1.17) 0.68(0.32-1.45)FGFR1 rs6987534 0.91(0.60-1.39) 0.70(0.34-1.44) 0.79(0.50-1.25) 0.75(0.35-1.59)NBS1 rs9995 0.95(0.61-1.48) 0.88(0.49-1.57) 0.97(0.60-1.58) 0.83(0.45-1.54)NBS1 or NBN rs1805787 1.06(0.21-5.30) 0.96(0.18-5.03)8q24 rs13281615 0.93(0.59-1.49) 1.29(0.73-2.30) 1.09(0.66-1.81) 1.33(0.72-2.46)MYC rs3891248 0.95(0.61-1.51) 1.07(0.59-1.96) 0.91(0.56-1.48) 1.01(0.53-1.91)CDKN2A rs3731239 1.00(0.63-1.58) 0.26(0.03-2.00) 0.96(0.58-1.57) 0.20(0.03-1.59)MCS5A6 rs2182317 1.14(0.74-1.76) 0.21(0.03-1.64) 1.16(0.72-1.86) 0.13(0.02-1.03)FLJ45983 rs1149901 1.10(0.61-1.99) 2.16(0.36-13.12) 1.04(0.56-1.95) 1.82(0.29-11.44)GATA3 rs570613 0.65(0.42-1.01) 0.84(0.45-1.56) 0.73(0.46-1.18) 0.87(0.45-1.66)GATA3 rs422628 0.74(0.38-1.44) 6.18(0.56-68.78) 0.65(0.32-1.33) 7.36(0.63-85.76)FGFR2 rs11200014 1.41(0.92-2.14) 0.94(0.41-2.15) 1.47(0.93-2.31) 0.79(0.31-1.98)FGFR2 rs2981579 1.01(0.63-1.60) 1.27(0.71-2.25) 1.09(0.66-1.79) 1.36(0.72-2.55)FGFR2 rs1078806 1.31(0.86-2.00) 0.91(0.40-2.07) 1.39(0.88-2.19) 0.76(0.30-1.92)FGFR2 rs1219648 1.26(0.81-1.96) 1.03(0.54-1.98) 1.33(0.83-2.15) 1.00(0.48-2.06)FGFR2 rs2420946 1.33(0.86-2.06) 1.02(0.53-1.94) 1.48(0.92-2.38) 0.96(0.47-1.98)FGFR2 rs2981582 1.32(0.86-2.01) 0.76(0.35-1.65) 1.42(0.90-2.24) 0.70(0.30-1.67)FGFR2 rs10510126 1.36(0.72-2.58) 1.49(0.74-2.98)LSP1 rs661348 1.70(1.06-2.75) 2.20(1.23-3.94) 1.45(0.87-2.42) 1.81(0.98-3.35)LSP1 rs3817198 1.03(0.65-1.65) 2.96(1.11-7.90) 1.09(0.67-1.80) 1.49(0.50-4.40)H19 rs2107425 0.44(0.28-0.70) 0.53(0.30-0.92) 0.42(0.26-0.69) 0.57(0.31-1.04)CCND1 rs3212891 0.86(0.53-1.39) 1.85(0.43-7.87) 0.92(0.55-1.53) 1.54(0.33-7.11)CCND1 rs678653 0.93(0.57-1.52) 1.89(0.44-8.06) 1.03(0.61-1.71) 1.59(0.34-7.35)NUMA1 rs3750913 0.56(0.27-1.17) 0.65(0.30-1.40)PGR rs500760 0.96(0.62-1.49) 1.99(0.63-6.26) 0.83(0.51-1.33) 2.10(0.64-6.90)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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PGR rs511298 0.98(0.63-1.54) 1.84(0.53-6.44) 0.83(0.51-1.36) 1.66(0.46-5.99)PGR rs660149 2.48(1.02-6.03) 1.88(0.69-5.13)PGR rs2020876 0.39(0.05-3.15) 0.58(0.07-4.95)PGR rs7116336 1.14(0.74-1.77) 1.52(0.51-4.51) 1.02(0.64-1.64) 1.14(0.34-3.78)PGR rs11571171 0.91(0.57-1.44) 2.34(0.51-10.64) 0.83(0.50-1.37) 2.35(0.50-11.05)PGR rs566351 1.02(0.65-1.61) 1.06(0.28-4.01) 0.94(0.58-1.54) 1.22(0.31-4.84)PGR rs506487 1.59(0.14-17.6) 1.37(0.12-16.1)PGR rs518162 2.70(1.09-6.69) 2.17(0.78-6.05)MMP8 rs1892886 1.10(0.63-1.94) 0.64(0.07-5.53) 0.94(0.50-1.74) 0.53(0.06-4.91)CDKN1B rs34330 1.47(0.89-2.41) 1.92(1.08-3.41) 1.42(0.83-2.41) 1.87(1.02-3.43)IGF1 rs2946834 0.77(0.49-1.23) 0.83(0.48-1.44) 0.67(0.40-1.12) 0.73(0.40-1.33)IGF1 rs5742714 0.56(0.33-0.94) 1.41(0.55-3.60) 0.58(0.33-1.00) 1.27(0.48-3.39)IGF1 rs6214 0.69(0.42-1.13) 1.22(0.72-2.04) 0.71(0.41-1.21) 1.24(0.71-2.16)IGF1 rs1520220 0.88(0.56-1.38) 0.76(0.43-1.35) 0.78(0.48-1.27) 0.70(0.38-1.30)IGF1 rs10745940 0.88(0.56-1.38) 0.77(0.43-1.37) 0.78(0.48-1.27) 0.70(0.38-1.31)IGF1 rs5742694 0.57(0.34-0.97) 1.23(0.46-3.28) 0.60(0.34-1.05) 1.10(0.39-3.10)IGF1 rs978458 0.88(0.56-1.39) 0.75(0.42-1.34) 0.78(0.48-1.28) 0.69(0.37-1.28)IGF1 rs5742667 0.91(0.58-1.42) 0.74(0.41-1.31) 0.82(0.50-1.34) 0.68(0.37-1.27)IGF1 rs2373721 0.54(0.32-0.91) 1.51(0.59-3.91) 0.56(0.32-0.98) 1.36(0.50-3.66)IGF1 rs7136446 0.54(0.32-0.91) 1.51(0.59-3.91) 0.56(0.32-0.98) 1.36(0.50-3.66)IGF1 rs9989002 0.51(0.30-0.87) 1.68(0.60-4.74) 0.55(0.31-0.97) 1.55(0.52-4.61)IGF1 rs5742632 1.02(0.65-1.60) 0.71(0.39-1.31) 0.90(0.55-1.47) 0.69(0.36-1.31)IGF1 rs2195240 1.02(0.65-1.60) 0.75(0.41-1.37) 0.90(0.55-1.47) 0.73(0.38-1.38)IGF1 rs5742629 1.03(0.66-1.62) 0.75(0.41-1.37) 0.91(0.56-1.49) 0.73(0.38-1.37)IGF1 rs7956547 0.58(0.34-0.98) 1.73(0.61-4.87) 0.60(0.34-1.05) 1.58(0.53-4.71)IGF1 rs4764698 1.06(0.69-1.61) 0.84(0.38-1.85) 1.03(0.65-1.63) 0.74(0.31-1.73)IGF1 rs10778176 1.08(0.69-1.70) 0.75(0.41-1.35) 0.95(0.58-1.55) 0.71(0.38-1.34)IGF1 rs2162679 1.01(0.65-1.56) 1.02(0.53-1.94) 0.96(0.60-1.53) 0.87(0.44-1.74)IGF1 rs35765 1.27(0.61-2.63) 1.23(0.57-2.64)IGF1 rs7965399 1.21(0.79-1.84) 1.33(0.63-2.83) 1.16(0.74-1.83) 1.15(0.51-2.61)IGF1 rs855211 1.02(0.67-1.57) 1.40(0.72-2.70) 1.00(0.63-1.59) 1.21(0.60-2.45)BRCA2 rs144848 0.86(0.56-1.32) 1.90(0.85-4.21) 0.80(0.50-1.27) 2.24(0.93-5.35)BRCA2 rs4942485 1.28(0.55-2.99) 1.19(0.49-2.90)IRS2 rs9515118 1.17(0.76-1.80) 1.24(0.61-2.55) 1.17(0.73-1.86) 1.06(0.49-2.30)IRS2 rs4773082 1.08(0.71-1.65) 1.28(0.58-2.80) 0.96(0.61-1.51) 1.24(0.54-2.87)IRS2 rs2289046 0.89(0.57-1.40) 0.65(0.35-1.20) 0.98(0.60-1.61) 0.80(0.41-1.54)IRS2 rs754204 0.91(0.59-1.38) 1.28(0.61-2.66) 0.79(0.50-1.25) 1.13(0.51-2.54)IRS2 rs7987237 1.26(0.82-1.94) 1.56(0.73-3.35) 1.23(0.77-1.96) 1.45(0.64-3.28)IRS2 rs12584136 0.65(0.28-1.51) 0.52(0.21-1.32)IRS2 rs9559648 1.06(0.69-1.63) 1.65(0.64-4.25) 0.97(0.61-1.54) 1.52(0.55-4.22)IRS2 rs9559654 1.06(0.69-1.65) 2.12(0.79-5.64) 0.99(0.62-1.60) 1.82(0.63-5.29)IRS2 rs7997595 1.17(0.76-1.80) 1.52(0.77-3.04) 1.05(0.66-1.69) 1.53(0.73-3.22)IRS2 rs7981705 0.68(0.25-1.82) 1.02(0.36-2.89)IRS2 rs4773092 0.74(0.47-1.17) 0.60(0.34-1.06) 0.79(0.48-1.28) 0.75(0.40-1.38)ESR2 rs1255998 1.25(0.78-1.98) 1.00(0.55-1.81) 1.35(0.82-2.23) 1.16(0.61-2.21)ESR2 rs8018687 1.10(0.64-1.89) 1.06(0.11-10.32) 1.07(0.59-1.95) 0.93(0.09-9.32)ESR2 rs928554 0.86(0.56-1.33) 0.92(0.49-1.72) 0.86(0.54-1.37) 0.81(0.40-1.62)ESR2 rs1152579 0.85(0.55-1.31) 0.92(0.49-1.71) 0.85(0.53-1.35) 0.80(0.40-1.60)ESR2 rs1256049 0.71(0.46-1.10) 1.15(0.54-2.43) 0.80(0.50-1.29) 1.28(0.57-2.84)ESR2 rs1256030 1.03(0.67-1.60) 0.95(0.51-1.79) 1.01(0.63-1.62) 0.86(0.43-1.72)ESR2 rs1271572 1.03(0.67-1.60) 0.86(0.45-1.64) 1.02(0.64-1.64) 0.75(0.37-1.54)XRCC3 rs861539 1.42(0.72-2.82) 1.37(0.65-2.88)XRCC3 rs1799796 1.08(0.70-1.66) 1.02(0.52-2.00) 1.03(0.65-1.65) 0.97(0.47-2.00)XRCC3 rs1799794 0.92(0.57-1.49) 0.95(0.54-1.66) 0.87(0.52-1.48) 0.91(0.50-1.67)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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AKT1 rs2494744 1.00(0.65-1.54) 0.92(0.48-1.77) 1.06(0.67-1.69) 1.10(0.55-2.20)AKT1 rs2498787 0.81(0.53-1.26) 0.88(0.46-1.67) 0.86(0.54-1.37) 1.07(0.54-2.12)CYP20 rs4646 1.38(0.89-2.14) 1.03(0.48-2.20) 1.27(0.80-2.02) 0.86(0.37-1.97)CYP19 rs10046 1.13(0.69-1.86) 1.49(0.84-2.64) 1.02(0.60-1.73) 1.25(0.67-2.31)CYP21 rs727479 1.37(0.89-2.11) 1.06(0.52-2.17) 1.34(0.85-2.12) 0.91(0.42-1.97)MAP2K1 rs7174378 0.95(0.59-1.54) 1.09(0.62-1.92) 1.21(0.72-2.04) 1.23(0.66-2.28)MAP2K1 rs7181936 0.90(0.57-1.41) 1.61(0.92-2.83) 0.90(0.55-1.46) 1.53(0.83-2.81)MAP2K1 rs28620576 1.11(0.72-1.71) 1.69(0.85-3.34) 1.23(0.78-1.95) 1.49(0.71-3.13)MAP2K1 rs8039880 0.81(0.52-1.27) 0.96(0.54-1.71) 0.87(0.54-1.42) 1.08(0.58-2.00)CYP1A1 rs1048943 1.24(0.82-1.89) 0.42(0.09-1.86) 1.30(0.82-2.04) 0.50(0.11-2.36)IGF1R rs4966007 1.00(0.65-1.56) 1.05(0.57-1.91) 1.10(0.68-1.78) 1.20(0.63-2.29)IGF1R rs8028620 1.02(0.62-1.66) 1.31(0.76-2.26) 1.03(0.61-1.74) 1.34(0.74-2.42)IGF1R rs4966009 0.99(0.64-1.55) 1.00(0.54-1.86) 1.10(0.68-1.78) 1.16(0.60-2.24)IGF1R rs8027457 1.11(0.68-1.82) 1.33(0.76-2.30) 1.15(0.68-1.94) 1.35(0.74-2.44)IGF1R rs4966012 0.89(0.58-1.38) 1.53(0.79-2.97) 0.90(0.56-1.43) 1.67(0.81-3.43)IGF1R rs1574213 0.80(0.51-1.25) 1.93(0.72-5.13) 0.89(0.55-1.43) 2.08(0.71-6.13)IGF1R rs11630479 0.86(0.56-1.32) 1.33(0.67-2.66) 0.93(0.59-1.48) 1.51(0.71-3.21)IGF1R rs4966013 1.27(0.77-2.09) 1.54(0.87-2.73) 1.48(0.87-2.53) 1.76(0.95-3.27)IGF1R rs4966015 0.66(0.42-1.02) 0.63(0.21-1.94) 0.65(0.40-1.04) 0.68(0.21-2.14)IGF1R rs8032477 0.81(0.51-1.31) 0.80(0.46-1.41) 0.86(0.51-1.44) 0.76(0.42-1.40)IGF1R rs11634241 1.05(0.69-1.60) 0.90(0.43-1.88) 1.22(0.77-1.93) 0.79(0.35-1.78)IGF1R rs932071 0.99(0.64-1.51) 0.94(0.36-2.43) 1.26(0.79-2.01) 0.59(0.19-1.82)IGF1R rs875686 1.01(0.66-1.55) 1.16(0.51-2.60) 1.25(0.79-1.99) 0.88(0.33-2.33)IGF1R rs1567811 1.09(0.70-1.70) 1.05(0.57-1.95) 1.23(0.76-1.99) 0.95(0.48-1.91)IGF1R rs11632952 0.99(0.65-1.52) 0.90(0.35-2.31) 1.30(0.82-2.08) 0.53(0.17-1.61)IGF1R rs4966024 0.94(0.57-1.54) 1.07(0.60-1.89) 1.10(0.65-1.87) 1.02(0.54-1.91)IGF1R rs8041224 1.11(0.71-1.74) 0.91(0.49-1.68) 1.26(0.77-2.04) 0.90(0.45-1.77)IGF1R rs7175052 1.12(0.72-1.75) 0.80(0.43-1.50) 1.23(0.76-1.97) 0.75(0.38-1.51)IGF1R rs2137680 1.23(0.75-2.01) 0.95(0.53-1.70) 1.38(0.82-2.35) 0.95(0.50-1.79)IGF1R rs12439557 1.20(0.78-1.83) 0.88(0.42-1.88) 1.47(0.93-2.33) 0.78(0.34-1.81)IGF1R rs4966028 0.78(0.47-1.28) 0.89(0.24-3.32) 0.77(0.45-1.31) 1.14(0.29-4.51)IGF1R rs907806 0.71(0.43-1.17) 1.25(0.32-4.93) 0.69(0.40-1.18) 1.72(0.38-7.66)IGF1R rs8041953 0.79(0.49-1.27) 0.99(0.26-3.75) 0.83(0.49-1.38) 1.38(0.34-5.65)IGF1R rs2670501 0.84(0.54-1.30) 0.74(0.39-1.38) 0.82(0.51-1.31) 0.65(0.33-1.29)IGF1R rs4246340 1.01(0.62-1.64) 1.65(0.94-2.90) 1.06(0.63-1.79) 1.62(0.88-2.96)IGF1R rs2684777 1.30(0.81-2.07) 1.44(0.77-2.67) 1.33(0.80-2.20) 1.42(0.72-2.79)IGF1R rs8030950 1.19(0.78-1.81) 0.41(0.12-1.39) 1.16(0.74-1.83) 0.46(0.13-1.63)IGF1R rs12594847 0.91(0.59-1.41) 0.70(0.35-1.37) 0.94(0.59-1.49) 0.65(0.31-1.36)IGF1R rs2684781 0.78(0.51-1.20) 0.58(0.30-1.14) 0.78(0.49-1.25) 0.53(0.26-1.09)IGF1R rs1521481 1.06(0.69-1.62) 0.70(0.28-1.77) 0.98(0.62-1.56) 0.81(0.31-2.11)IGF1R rs4966035 0.69(0.44-1.10) 0.74(0.42-1.31) 0.61(0.37-1.01) 0.75(0.41-1.39)IGF1R rs4966036 1.34(0.84-2.12) 1.63(0.89-3.00) 1.34(0.82-2.21) 1.72(0.89-3.32)IGF1R rs7165875 0.69(0.44-1.10) 0.74(0.42-1.31) 0.61(0.37-1.01) 0.76(0.42-1.40)IGF1R rs3743259 0.62(0.39-0.99) 0.76(0.44-1.34) 0.55(0.33-0.90) 0.79(0.43-1.44)IGF1R rs3743260 1.12(0.70-1.79) 0.29(0.04-2.29) 1.07(0.65-1.77) 0.32(0.04-2.54)IGF1R rs2684810 1.03(0.67-1.57) 0.66(0.28-1.56) 0.86(0.54-1.36) 0.68(0.28-1.66)IGF1R rs4966039 0.97(0.62-1.51) 0.67(0.19-2.39) 0.85(0.53-1.36) 0.68(0.18-2.50)IGF1R rs2684805 1.10(0.69-1.75) 1.46(0.83-2.57) 1.10(0.67-1.81) 1.35(0.73-2.48)IGF1R rs2684803 1.55(0.99-2.42) 1.84(1.00-3.39) 1.69(1.05-2.73) 1.69(0.87-3.28)IGF1R rs1546713 1.53(0.98-2.39) 1.83(0.99-3.38) 1.66(1.03-2.68) 1.67(0.86-3.25)IGF1R rs7166558 1.56(1.00-2.43) 1.85(1.00-3.42) 1.72(1.06-2.78) 1.71(0.88-3.33)IGF1R rs2229765 1.58(1.01-2.47) 1.92(1.04-3.54) 1.75(1.08-2.84) 1.77(0.91-3.44)IGF1R rs11635251 0.95(0.62-1.46) 0.73(0.36-1.51) 0.85(0.54-1.35) 0.67(0.32-1.40)IGF1R rs8038056 0.90(0.59-1.38) 0.50(0.22-1.10) 0.98(0.62-1.56) 0.58(0.24-1.40)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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IGF1R rs12916884 1.01(0.66-1.54) 0.54(0.26-1.12) 0.94(0.59-1.49) 0.53(0.25-1.14)IGF1R rs7173377 0.99(0.65-1.52) 0.56(0.26-1.20) 0.94(0.60-1.49) 0.60(0.26-1.38)IGF1R rs7166565 0.98(0.64-1.50) 0.59(0.28-1.24) 0.96(0.61-1.52) 0.67(0.30-1.50)IGF1R rs939626 0.86(0.56-1.33) 0.43(0.16-1.15) 0.81(0.51-1.30) 0.45(0.15-1.37)IGF1R rs12437963 1.61(1.01-2.55) 2.09(1.15-3.81) 1.91(1.15-3.17) 2.04(1.06-3.92)IGF1R rs2684788 1.25(0.77-2.05) 1.49(0.84-2.66) 1.49(0.87-2.55) 1.64(0.88-3.05)IGF1R rs1815009 1.56(0.95-2.57) 1.70(0.95-3.03) 1.95(1.13-3.38) 1.83(0.98-3.45)A2BP1 rs7203563 1.05(0.68-1.62) 1.39(0.52-3.75) 1.12(0.70-1.79) 1.41(0.45-4.45)TNRC9/LOC643714 rs8051542 1.61(1.06-2.46) 2.56(1.06-6.19) 1.45(0.92-2.29) 2.09(0.81-5.39)TNRC9/LOC643714 rs12443621 0.87(0.57-1.35) 0.99(0.52-1.88) 0.87(0.55-1.39) 1.09(0.55-2.19)TNRC9 or TOX3 rs3803662 0.45(0.29-0.69) 0.36(0.18-0.72) 0.42(0.26-0.68) 0.24(0.11-0.55)ATP1B2 rs1641512 1.25(0.79-1.96) 1.23(0.68-2.23) 1.33(0.82-2.16) 1.36(0.71-2.59)TP53 rs9894946 0.47(0.16-1.37) 0.38(0.13-1.15)TP53 rs1614984 1.14(0.74-1.75) 0.75(0.37-1.55) 1.13(0.71-1.78) 0.92(0.41-2.04)TP53 rs1042522 1.01(0.66-1.56) 0.56(0.27-1.15) 0.99(0.63-1.58) 0.60(0.27-1.33)WDR79 rs2287499 0.80(0.52-1.23) 0.97(0.40-2.37) 0.79(0.50-1.24) 0.97(0.35-2.69)WDR79 rs17885803 0.87(0.50-1.52) 3.12(0.43-22.40) 0.92(0.51-1.65) 2.60(0.34-19.76)WDR79 rs2287498 0.81(0.53-1.25) 0.97(0.40-2.38) 0.79(0.50-1.25) 0.98(0.35-2.70)HER2 rs1565923 1.44(0.91-2.28) 1.33(0.71-2.52) 1.36(0.83-2.24) 1.15(0.58-2.27)ERBB rs1810132 1.45(0.92-2.30) 1.34(0.71-2.54) 1.39(0.85-2.29) 1.16(0.59-2.30)HER2 rs3809717 0.95(0.62-1.46) 1.25(0.59-2.65) 0.87(0.54-1.38) 1.14(0.51-2.51)ITGB3 rs3809865 1.22(0.80-1.87) 1.07(0.38-3.03) 1.18(0.75-1.86) 1.17(0.40-3.45)ITGA3 rs1062484 0.63(0.07-5.44) 0.57(0.06-5.86)AXIN2 rs7210356 1.22(0.76-1.94) 0.54(0.12-2.48) 1.26(0.76-2.09) 0.55(0.11-2.76)AXIN2 rs4791171 0.64(0.42-0.98) 0.40(0.19-0.85) 0.60(0.38-0.94) 0.35(0.15-0.80)AXIN2 rs11079571 1.70(1.11-2.61) 1.81(0.88-3.71) 1.59(1.00-2.53) 2.61(1.18-5.77)AXIN2 rs3923087 0.61(0.40-0.94) 0.52(0.25-1.08) 0.57(0.36-0.91) 0.48(0.21-1.06)AXIN2 rs3923086 0.68(0.42-1.09) 0.56(0.12-2.62) 0.72(0.43-1.21) 0.52(0.11-2.53)GPX4 rs4807542 0.93(0.59-1.47) 1.50(0.66-3.45) 0.98(0.60-1.59) 1.71(0.68-4.27)MAP2K2 rs350916 1.19(0.77-1.84) 1.30(0.69-2.44) 1.41(0.88-2.26) 1.30(0.66-2.55)MAP2K2 rs350913 1.26(0.81-1.96) 1.29(0.70-2.39) 1.48(0.92-2.39) 1.23(0.64-2.37)MAP2K2 rs7258366 1.24(0.81-1.90) 1.10(0.54-2.24) 1.39(0.87-2.20) 1.19(0.56-2.51)MAP2K2 rs350894 0.97(0.62-1.51) 1.21(0.67-2.20) 1.20(0.74-1.95) 1.25(0.66-2.35)MAP2K2 rs12459484 1.35(0.87-2.09) 1.09(0.58-2.05) 1.42(0.88-2.28) 1.28(0.66-2.51)ICAM5 rs1056538 0.84(0.54-1.29) 1.26(0.65-2.45) 0.88(0.55-1.40) 1.11(0.55-2.24)CCNE1 rs997669 1.07(0.61-1.88) 1.61(0.29-8.90) 1.19(0.66-2.16) 2.14(0.30-15.14)XRCC1 rs25487 1.57(1.03-2.38) 1.37(0.52-3.61) 1.47(0.94-2.31) 1.14(0.39-3.36)PTGIS rs6095541 0.52(0.27-1.03) 2.94(0.18-47.35) 0.60(0.30-1.21) 1.83(0.11-30.11)PTGIS rs6095543 0.69(0.42-1.12) 1.16(0.36-3.79) 0.73(0.43-1.23) 0.81(0.21-3.20)PTGIS rs693649 0.97(0.63-1.50) 0.77(0.41-1.45) 0.89(0.55-1.43) 0.93(0.47-1.83)AURKA rs8173 0.87(0.56-1.34) 1.56(0.82-2.96) 0.85(0.53-1.37) 1.69(0.85-3.38)AURKA rs10485805 0.79(0.51-1.22) 1.81(0.76-4.30) 0.79(0.50-1.27) 1.89(0.73-4.91)AURKA rs6024840 1.25(0.82-1.92) 0.88(0.43-1.83) 1.44(0.91-2.27) 0.84(0.38-1.83)AURKA rs911160 1.29(0.84-1.97) 0.89(0.43-1.85) 1.49(0.94-2.36) 0.84(0.38-1.84)AURKA rs2298016 1.06(0.69-1.64) 1.02(0.53-1.97) 1.12(0.70-1.78) 1.00(0.50-2.01)AURKA rs2273535 1.12(0.73-1.74) 1.05(0.54-2.03) 1.18(0.74-1.89) 1.03(0.51-2.08)COMT rs4680 0.83(0.55-1.26) 0.92(0.40-2.16) 0.80(0.51-1.25) 0.91(0.35-2.35)CHEK2 rs9608698 0.79(0.51-1.22) 2.09(0.86-5.08) 0.83(0.52-1.32) 1.86(0.73-4.75)PHKA1 rs3012642 1.03(0.65-1.63) 0.96(0.26-3.55) 　 1.02(0.63-1.66) 0.93(0.24-3.51)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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Table 10-1. Association of 384 SNPs with TN breast cancer risk　　 TN (additive model)


MTHFR rs1801131 1.02(0.74-1.41) 0.60(0.25-1.43) 0.95(0.66-1.37) 0.71(0.29-1.76)RIZ1 or PRDM2 rs2235515 1.17(0.78-1.76) 1.15(0.74-1.77) 1.07(0.74-1.55) 0.75(0.46-1.24)HSD11B1 rs4393158 0.79(0.50-1.25) 0.86(0.54-1.36) 0.96(0.67-1.37) 1.23(0.74-2.05)HSD11B1 rs17317033 2.22(0.74-6.69) 1.90(0.52-7.00)HSD11B1 rs2235543 1.00(0.72-1.38) 0.84(0.54-1.33) 0.96(0.67-1.37) 0.84(0.50-1.40)HSD11B1 rs11807619 0.81(0.58-1.13) 0.81(0.35-1.86) 0.85(0.59-1.22) 0.62(0.22-1.75)HSD11B1 rs932335 0.76(0.54-1.08) 0.93(0.38-2.27) 0.83(0.57-1.22) 0.63(0.20-1.95)2p(19150424) rs4666451 1.08(0.61-1.94) 0.95(0.48-1.88)CYP1B1 rs1800440 2.45(0.45-13.44) 1.39(0.19-10.4)CYP1B1 rs1056836 1.46(1.03-2.08) 3.34(0.64-17.38) 1.30(0.87-1.92) 2.90(0.54-15.7)ITGA6 rs17664 1.10(0.78-1.57) 0.86(0.32-2.30) 1.08(0.73-1.60) 0.96(0.31-2.96)ITGAv rs11902171 0.73(0.47-1.14) 2.35(0.43-12.90) 0.68(0.41-1.12) 3.43(0.35-33.9)BARD1 rs6759222 1.14(0.75-1.74) 1.23(0.25-6.16) 1.02(0.64-1.64) 0.82(0.14-5.05)BARD1 rs4673896 1.02(0.74-1.40) 0.72(0.45-1.15) 0.93(0.65-1.32) 0.68(0.40-1.14)BARD1 rs6717301 0.98(0.69-1.38) 0.91(0.60-1.38) 1.06(0.72-1.56) 1.13(0.71-1.81)BARD1 rs2229571 1.07(0.78-1.46) 0.69(0.42-1.14) 1.02(0.71-1.45) 0.71(0.41-1.24)BARD1 rs3768704 1.07(0.76-1.49) 0.91(0.60-1.39) 1.19(0.81-1.74) 1.07(0.67-1.73)BARD1 rs7591615 0.89(0.53-1.52) 2.41(0.22-26.69) 0.79(0.43-1.43) 1.24(0.08-20.1)BARD1 rs6435862 1.11(0.80-1.56) 2.24(0.92-5.43) 1.03(0.71-1.50) 1.50(0.56-4.03)2q35 rs13387042 0.87(0.59-1.29) 0.29(0.03-2.65) 1.01(0.65-1.57) 0.46(0.05-4.44)FGFR2 rs12505080 1.62(1.14-2.30) 1.19(0.77-1.85) 1.65(1.11-2.44) 1.31(0.81-2.13)FGFR2 rs7696175 0.85(0.60-1.22) 1.18(0.38-3.70) 0.95(0.64-1.41) 1.68(0.45-6.32)KIT rs2237038 1.05(0.75-1.46) 1.01(0.65-1.58) 1.10(0.76-1.60) 0.92(0.55-1.54)KIT rs981959 1.08(0.77-1.51) 1.03(0.65-1.62) 1.11(0.76-1.62) 0.91(0.54-1.54)KIT rs2237034 0.90(0.66-1.24) 0.81(0.42-1.57) 1.00(0.70-1.42) 0.83(0.38-1.79)KIT rs2237032 0.90(0.66-1.23) 0.69(0.38-1.25) 0.98(0.69-1.38) 0.70(0.35-1.40)KIT rs2237023 1.04(0.75-1.44) 1.73(1.09-2.74) 1.08(0.75-1.55) 1.29(0.76-2.18)KIT rs6810872 1.03(0.75-1.43) 1.70(1.07-2.70) 1.08(0.76-1.55) 1.26(0.74-2.13)KIT rs3134884 1.19(0.87-1.62) 1.75(0.89-3.44) 1.21(0.85-1.71) 1.38(0.65-2.90)KIT rs3111800 1.08(0.75-1.55) 1.44(0.94-2.21) 1.05(0.70-1.59) 1.23(0.76-1.99)KIT rs2237018 1.12(0.82-1.52) 0.87(0.47-1.58) 1.03(0.73-1.46) 0.79(0.40-1.56)KIT rs6843170 1.12(0.82-1.53) 0.95(0.52-1.73) 1.03(0.73-1.46) 0.88(0.45-1.72)KDR rs17709898 1.16(0.85-1.58) 1.20(0.66-2.18) 1.06(0.75-1.51) 1.15(0.59-2.23)KDR rs12505758 1.19(0.87-1.62) 0.63(0.31-1.30) 0.91(0.64-1.29) 0.55(0.25-1.20)KDR rs2168945 0.94(0.68-1.29) 1.01(0.64-1.58) 1.02(0.71-1.45) 1.39(0.82-2.34)KDR rs13136007 1.04(0.75-1.45) 0.99(0.65-1.53) 1.05(0.73-1.52) 1.02(0.62-1.65)KDR rs11732292 0.94(0.68-1.29) 1.00(0.64-1.58) 1.02(0.72-1.45) 1.35(0.80-2.28)KDR rs1870377 1.05(0.76-1.45) 0.97(0.63-1.49) 1.04(0.72-1.51) 0.99(0.61-1.61)KDR rs7673274 1.18(0.86-1.61) 0.95(0.52-1.75) 0.96(0.67-1.36) 0.76(0.38-1.49)KDR rs11133360 1.04(0.76-1.43) 0.91(0.58-1.44) 1.00(0.70-1.44) 0.94(0.57-1.57)STE or SULT1E1 rs3775775 1.15(0.72-1.81) 1.23(0.17-8.80) 1.16(0.70-1.92) 0.76(0.06-9.01)STE or SULT1E1 rs1881668 1.52(1.10-2.09) 1.22(0.76-1.96) 1.39(0.97-1.98) 1.12(0.66-1.92)ADH1B rs1042026 0.65(0.47-0.90) 0.98(0.41-2.34) 0.80(0.56-1.16) 0.93(0.33-2.62)5p12 rs4415084 1.01(0.72-1.42) 0.88(0.58-1.33) 1.07(0.73-1.57) 0.99(0.62-1.59)MRPS30 rs10941679 1.02(0.72-1.44) 1.07(0.71-1.62) 0.93(0.63-1.36) 0.94(0.59-1.49)5p14 rs7703618 0.95(0.70-1.30) 1.15(0.71-1.87) 0.99(0.70-1.40) 1.13(0.65-1.96)5p15 rs10035564 1.02(0.73-1.44) 0.96(0.63-1.47) 1.10(0.76-1.61) 0.93(0.57-1.50)5p(45321475bp) rs981782 0.97(0.71-1.34) 0.95(0.61-1.49) 1.03(0.71-1.48) 1.10(0.68-1.78)5q(52454339bp) rs30099 0.87(0.62-1.21) 1.34(0.86-2.08) 0.80(0.55-1.17) 1.35(0.82-2.23)MAP3K1 rs889312 0.86(0.61-1.20) 0.75(0.49-1.15) 0.82(0.56-1.20) 0.59(0.37-0.97)DHFR rs1677666 0.77(0.33-1.81) 0.67(0.26-1.74)APC rs11954856 0.72(0.52-1.01) 1.02(0.46-2.29) 0.74(0.51-1.08) 1.07(0.41-2.80)APC rs11241183 0.83(0.61-1.13) 0.82(0.47-1.42) 0.92(0.65-1.31) 0.82(0.45-1.50)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition..

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APC rs2439591 0.73(0.53-1.02) 1.03(0.47-2.24) 0.72(0.50-1.05) 1.10(0.44-2.75)APC rs2431512 0.78(0.57-1.06) 0.72(0.42-1.24) 0.83(0.58-1.17) 0.73(0.40-1.33)APC rs2431238 0.93(0.62-1.40) 1.40(0.47-4.22) 0.89(0.56-1.43) 2.29(0.55-9.53)APC rs454886 0.81(0.59-1.10) 1.02(0.62-1.71) 0.93(0.65-1.32) 1.30(0.74-2.27)APC rs501250 0.84(0.55-1.28) 1.67(0.52-5.32) 0.70(0.43-1.14) 3.11(0.61-16.0)APC rs2229992 0.84(0.62-1.15) 0.79(0.44-1.42) 0.88(0.62-1.25) 0.83(0.44-1.57)APC rs41116 0.82(0.60-1.11) 0.83(0.46-1.52) 0.85(0.60-1.21) 0.87(0.45-1.67)APC rs448475 0.82(0.60-1.12) 0.83(0.46-1.52) 0.86(0.60-1.22) 0.87(0.45-1.68)CDKN1A rs3176336 1.28(0.94-1.74) 0.88(0.50-1.57) 1.36(0.96-1.94) 1.17(0.63-2.20)CDKN1A rs1801270 0.73(0.52-1.04) 0.77(0.50-1.17) 0.62(0.42-0.92) 0.56(0.35-0.91)CCND3 rs2479717 0.96(0.63-1.47) 1.10(0.69-1.76)LSP1 rs381798 0.92(0.66-1.27) 0.75(0.48-1.16) 0.91(0.63-1.31) 0.82(0.50-1.35)ECHDC1 rs2180341 1.06(0.78-1.45) 1.47(0.85-2.54) 1.12(0.79-1.58) 1.27(0.67-2.40)ECHDC1 rs6569479 1.06(0.78-1.45) 1.47(0.85-2.55) 1.12(0.79-1.58) 1.27(0.67-2.40)ECHDC1 rs6569480 1.07(0.78-1.46) 1.47(0.85-2.54) 1.13(0.80-1.60) 1.27(0.67-2.40)ECHDC1 rs7776136 1.06(0.77-1.44) 1.46(0.84-2.53) 1.10(0.78-1.56) 1.27(0.67-2.41)ESR1 rs851984 1.13(0.79-1.63) 0.49(0.15-1.59) 1.08(0.72-1.62) 0.57(0.19-1.74)ESR1 rs851982 1.12(0.78-1.60) 0.49(0.15-1.58) 1.05(0.70-1.58) 0.57(0.19-1.74)ESR1 rs2881766 1.41(1.01-1.95) 0.93(0.59-1.48) 1.58(1.09-2.28) 0.97(0.58-1.64)ESR1 rs2077647 1.16(0.85-1.60) 1.09(0.69-1.73) 1.30(0.91-1.86) 1.32(0.79-2.21)ESR1 rs9322331 1.14(0.54-2.40) 1.16(0.54-2.48)ESR1 rs712221 1.03(0.74-1.44) 0.88(0.57-1.36) 1.02(0.70-1.48) 0.94(0.58-1.53)ESR1 rs1801132 0.73(0.51-1.04) 0.78(0.52-1.18) 0.73(0.49-1.08) 0.76(0.48-1.21)ESR1 rs3020314 1.04(0.76-1.44) 1.45(0.66-3.21) 1.10(0.76-1.58) 1.24(0.50-3.12)ESR1 rs3020377 1.06(0.76-1.46) 1.34(0.62-2.92) 1.13(0.79-1.63) 1.16(0.47-2.84)ESR1 rs3020390 0.87(0.64-1.20) 1.08(0.67-1.73) 0.91(0.64-1.30) 0.99(0.58-1.68)ESR1 rs3020317 0.82(0.59-1.15) 0.84(0.55-1.29) 0.87(0.60-1.26) 0.84(0.52-1.35)ESR1 rs3020394 0.91(0.66-1.25) 1.00(0.63-1.59) 0.95(0.67-1.36) 0.92(0.55-1.55)ESR1 rs3020396 0.89(0.65-1.23) 0.97(0.61-1.53) 0.95(0.66-1.36) 0.89(0.54-1.48)ESR1 rs3020401 0.89(0.65-1.23) 0.97(0.62-1.54) 0.95(0.66-1.36) 0.91(0.54-1.51)ESR1 rs1884051 1.07(0.75-1.53) 1.10(0.73-1.67) 1.03(0.69-1.53) 1.02(0.64-1.62)ESR1 rs1884054 0.95(0.70-1.30) 1.34(0.79-2.30) 1.03(0.72-1.46) 1.29(0.72-2.33)ESR1 rs3020405 0.97(0.71-1.33) 1.26(0.74-2.14) 1.05(0.74-1.49) 1.20(0.67-2.14)ESR1 rs726282 0.84(0.61-1.16) 0.75(0.48-1.18) 0.94(0.66-1.35) 0.79(0.47-1.31)ESR1 rs3020407 0.96(0.70-1.31) 1.45(0.88-2.39) 1.08(0.76-1.53) 1.32(0.75-2.32)ESR1 rs6905370 1.18(0.83-1.67) 1.33(0.87-2.04) 1.01(0.68-1.50) 1.31(0.81-2.11)ESR1 rs926778 1.37(0.99-1.89) 0.90(0.57-1.42) 1.47(1.02-2.12) 1.05(0.63-1.74)ESR1 rs3020366 1.28(0.91-1.80) 1.05(0.68-1.60) 1.12(0.76-1.64) 0.90(0.56-1.45)ESR1 rs2273206 1.38(1.01-1.88) 0.93(0.56-1.55) 1.51(1.06-2.14) 0.96(0.54-1.70)ESR1 rs750686 1.21(0.85-1.71) 1.08(0.71-1.64) 1.04(0.70-1.53) 0.89(0.55-1.43)ESR1 rs2228480 0.73(0.53-1.00) 0.44(0.18-1.08) 0.73(0.51-1.04) 0.48(0.16-1.39)ESR1 rs3798577 0.57(0.42-0.79) 0.60(0.38-0.96) 0.55(0.39-0.79) 0.64(0.38-1.08)ESR1 rs910416 0.77(0.56-1.06) 0.60(0.37-0.96) 0.80(0.56-1.15) 0.74(0.44-1.25)IGFBP3 rs2854744 1.34(0.97-1.85) 0.80(0.44-1.43) 1.34(0.93-1.92) 0.53(0.27-1.06)EGFR rs11770506 0.89(0.65-1.21) 0.71(0.42-1.19) 0.89(0.63-1.27) 0.70(0.39-1.25)EGFR rs4947974 0.92(0.68-1.26) 0.64(0.37-1.11) 0.85(0.60-1.21) 0.80(0.43-1.46)EGFR rs2110290 0.97(0.72-1.32) 0.69(0.39-1.20) 0.92(0.65-1.30) 0.89(0.48-1.65)EGFR rs12667668 0.99(0.72-1.34) 0.56(0.32-0.97) 1.02(0.72-1.45) 0.76(0.41-1.40)EGFR rs12718945 1.01(0.74-1.37) 0.61(0.35-1.05) 1.03(0.73-1.46) 0.86(0.47-1.58)EGFR rs6593207 1.22(0.90-1.66) 0.45(0.23-0.88) 1.23(0.87-1.74) 0.50(0.24-1.06)EGFR rs2072454 1.17(0.86-1.60) 0.63(0.38-1.06) 1.16(0.81-1.64) 0.69(0.39-1.21)EGFR rs11536635 1.21(0.87-1.67) 0.88(0.55-1.39) 1.28(0.89-1.84) 0.94(0.56-1.56)EGFR rs11977388 1.19(0.88-1.63) 0.65(0.37-1.12) 1.28(0.90-1.82) 0.70(0.38-1.27)EGFR rs10228436 1.33(0.97-1.84) 0.77(0.48-1.23) 1.53(1.06-2.20) 0.82(0.48-1.38)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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ABCB1 rs1045642 0.97(0.70-1.33) 1.22(0.77-1.92) 0.82(0.57-1.18) 1.11(0.67-1.83)ABCB1 rs7787082 0.94(0.67-1.31) 0.92(0.60-1.41) 0.89(0.61-1.30) 0.90(0.56-1.46)ABCB1 rs2091766 0.89(0.64-1.22) 0.89(0.57-1.38) 0.92(0.64-1.31) 0.92(0.56-1.51)ABCB1 rs1128503 0.94(0.67-1.30) 0.84(0.55-1.30) 0.94(0.65-1.35) 0.87(0.54-1.41)ABCB1 rs1922241 0.92(0.67-1.26) 0.87(0.55-1.37) 0.98(0.69-1.40) 0.91(0.54-1.52)ABCB1 rs868755 0.79(0.57-1.09) 1.18(0.75-1.85) 0.72(0.50-1.04) 1.18(0.71-1.94)ABCB1 rs2520464 0.99(0.71-1.37) 0.85(0.55-1.31) 0.99(0.69-1.42) 0.85(0.52-1.37)ABCB1 rs1202184 1.07(0.78-1.47) 0.77(0.48-1.24) 1.05(0.73-1.50) 0.78(0.46-1.32)ABCB1 rs12535512 0.92(0.66-1.30) 0.95(0.61-1.47) 1.02(0.70-1.48) 0.99(0.60-1.62)ABCB1 rs12720464 1.27(0.93-1.73) 1.76(0.92-3.38) 1.15(0.81-1.62) 1.73(0.86-3.48)ABCB1 rs1978095 1.34(0.99-1.83) 1.71(0.90-3.24) 1.22(0.86-1.72) 1.60(0.80-3.18)CDK6 rs3757823 1.42(1.00-2.01) 1.41(0.93-2.15) 1.32(0.89-1.95) 1.27(0.79-2.05)Q129R rs662 0.70(0.51-0.95) 0.53(0.32-0.88) 0.70(0.49-1.00) 0.51(0.29-0.90)L55M rs854560 0.86(0.54-1.36) 2.40(0.22-26.60) 0.81(0.48-1.36) 1.20(0.07-20.4)FGFR2 rs17157903 0.99(0.73-1.36) 0.92(0.47-1.81) 1.01(0.71-1.43) 1.18(0.55-2.52)MET rs2237710 1.03(0.75-1.43) 0.88(0.56-1.37) 1.08(0.75-1.55) 0.97(0.59-1.59)MET rs2299437 1.05(0.77-1.44) 1.03(0.64-1.67) 1.05(0.73-1.49) 1.15(0.68-1.95)MET rs10248537 1.05(0.77-1.44) 1.03(0.64-1.67) 1.05(0.73-1.49) 1.15(0.68-1.95)MET rs38855 1.14(0.82-1.59) 1.29(0.85-1.97) 1.24(0.86-1.80) 1.32(0.83-2.12)MET rs38858 1.16(0.83-1.61) 1.30(0.85-1.98) 1.27(0.88-1.84) 1.34(0.84-2.14)MET rs13223756 1.11(0.81-1.51) 0.86(0.49-1.49) 1.21(0.85-1.72) 0.79(0.42-1.47)MET rs2299440 1.10(0.81-1.51) 0.85(0.49-1.49) 1.20(0.84-1.71) 0.78(0.42-1.46)MET rs183642 1.35(0.94-1.93) 1.00(0.67-1.52) 1.35(0.91-2.02) 0.82(0.51-1.31)MET rs41736 1.37(0.95-1.96) 1.01(0.67-1.53) 1.37(0.92-2.04) 0.82(0.52-1.31)MET rs41739 1.40(0.98-2.01) 1.01(0.67-1.53) 1.41(0.94-2.10) 0.85(0.53-1.35)TBXAS1 rs6971207 1.35(0.98-1.85) 1.52(0.93-2.46) 1.31(0.92-1.87) 1.39(0.81-2.36)FGFR1 rs2304000 1.07(0.78-1.47) 0.91(0.55-1.50) 1.22(0.86-1.73) 0.87(0.50-1.54)FGFR1 rs4647907 1.06(0.77-1.45) 0.94(0.57-1.55) 1.19(0.84-1.69) 0.89(0.50-1.57)FGFR1 rs2956724 0.81(0.59-1.10) 1.07(0.61-1.88) 0.78(0.55-1.11) 0.98(0.53-1.81)FGFR1 rs2978073 0.76(0.55-1.03) 1.13(0.65-1.97) 0.72(0.51-1.02) 1.01(0.55-1.86)FGFR1 rs6983315 0.93(0.67-1.27) 1.29(0.82-2.04) 0.94(0.66-1.34) 1.30(0.77-2.18)FGFR1 rs6987534 0.97(0.71-1.33) 1.17(0.73-1.87) 1.00(0.70-1.43) 1.24(0.73-2.11)NBS1 rs9995 1.10(0.80-1.52) 0.62(0.39-0.97) 1.26(0.87-1.81) 0.49(0.29-0.84)NBS1 or NBN rs1805787 0.81(0.23-2.89) 0.61(0.15-2.47)8q24 rs13281615 1.07(0.76-1.51) 1.25(0.81-1.94) 1.23(0.84-1.80) 1.14(0.70-1.86)MYC rs3891248 0.96(0.69-1.34) 0.90(0.57-1.41) 1.21(0.84-1.76) 0.96(0.57-1.60)CDKN2A rs3731239 0.94(0.67-1.32) 0.79(0.32-1.96) 0.92(0.62-1.34) 0.52(0.18-1.53)MCS5A6 rs2182317 0.95(0.69-1.32) 1.12(0.53-2.38) 0.98(0.67-1.42) 1.04(0.47-2.32)EHMT1 rs4634736 2.45(0.45-13.44) 2.60(0.42-16.2)FLJ45983 rs1149901 0.85(0.54-1.34) 0.40(0.04-3.81) 0.84(0.51-1.38) 0.86(0.14-5.36)GATA3 rs570613 0.53(0.39-0.73) 0.64(0.40-1.02) 0.65(0.46-0.93) 0.72(0.43-1.21)GATA3 rs422628 0.75(0.47-1.21) 1.18(0.07-18.89) 0.80(0.48-1.33) 1.45(0.09-23.5)FGFR2 rs11200014 0.94(0.69-1.29) 0.71(0.39-1.30) 0.99(0.69-1.40) 0.80(0.42-1.52)FGFR2 rs2981579 1.11(0.80-1.55) 1.06(0.68-1.65) 1.01(0.69-1.46) 1.15(0.71-1.87)FGFR2 rs1078806 0.96(0.71-1.31) 0.64(0.34-1.20) 1.03(0.73-1.47) 0.73(0.38-1.42)FGFR2 rs1219648 1.05(0.77-1.44) 0.94(0.59-1.49) 1.01(0.71-1.45) 1.04(0.62-1.74)FGFR2 rs2420946 1.11(0.81-1.53) 1.01(0.64-1.58) 1.07(0.75-1.54) 1.10(0.67-1.82)FGFR2 rs2981582 1.23(0.90-1.68) 0.82(0.48-1.41) 1.18(0.83-1.69) 0.93(0.53-1.65)FGFR2 rs10510126 1.21(0.74-1.97) 1.40(0.81-2.43)LSP1 rs661348 1.13(0.82-1.56) 0.83(0.52-1.32) 1.12(0.78-1.61) 0.69(0.41-1.17)LSP1 rs3817198 0.89(0.63-1.26) 0.78(0.28-2.23) 0.91(0.62-1.33) 0.70(0.22-2.17)H19 rs2107425 0.80(0.57-1.13) 0.76(0.50-1.17) 0.78(0.53-1.15) 0.72(0.45-1.16)CCND1 rs3212891 0.93(0.66-1.31) 1.44(0.43-4.77) 0.83(0.56-1.23) 1.39(0.39-4.96)CCND1 rs678653 1.00(0.71-1.42) 1.22(0.35-4.26) 0.94(0.63-1.39) 1.12(0.29-4.31)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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NUMA1 rs3750913 1.16(0.75-1.79) 0.62(0.06-6.84) 1.01(0.62-1.65) 0.66(0.06-7.33)PGR rs500760 0.88(0.64-1.21) 1.32(0.50-3.49) 0.86(0.60-1.23) 1.70(0.65-4.47)PGR rs511298 0.93(0.67-1.29) 1.38(0.49-3.87) 0.95(0.66-1.38) 1.65(0.58-4.74)PGR rs660149 0.80(0.33-1.99) 0.81(0.30-2.15)PGR rs2020876 0.45(0.12-1.71) 0.38(0.07-1.91)PGR rs7116336 0.96(0.70-1.33) 1.09(0.46-2.62) 0.93(0.65-1.35) 1.19(0.49-2.91)PGR rs11571171 0.96(0.69-1.34) 2.45(0.73-8.25) 0.93(0.64-1.35) 3.02(0.87-10.5)PGR rs566351 1.04(0.75-1.44) 1.09(0.42-2.88) 0.99(0.68-1.44) 1.44(0.52-3.98)PGR rs506487 0.61(0.06-6.71) 0.69(0.06-7.69)PGR rs518162 0.88(0.35-2.21) 0.88(0.33-2.38)MMP8 rs1892886 1.22(0.81-1.84) 0.50(0.10-2.59) 1.03(0.64-1.64) 0.56(0.11-3.00)CDKN1B rs34330 1.18(0.84-1.66) 1.30(0.86-1.97) 1.20(0.82-1.76) 1.19(0.75-1.89)IGF1 rs2946834 0.83(0.59-1.17) 0.79(0.52-1.19) 0.81(0.55-1.20) 0.73(0.46-1.16)IGF1 rs5742714 1.08(0.78-1.50) 0.88(0.38-2.02) 1.00(0.69-1.45) 0.92(0.38-2.24)IGF1 rs6214 1.01(0.71-1.44) 1.11(0.74-1.66) 0.96(0.64-1.44) 1.06(0.67-1.67)IGF1 rs1520220 1.05(0.76-1.47) 0.79(0.51-1.20) 1.01(0.69-1.47) 0.71(0.44-1.16)IGF1 rs10745940 1.05(0.75-1.46) 0.80(0.52-1.22) 1.01(0.70-1.47) 0.72(0.44-1.17)IGF1 rs5742694 1.13(0.81-1.57) 0.80(0.34-1.89) 1.05(0.73-1.52) 0.84(0.34-2.12)IGF1 rs978458 1.07(0.77-1.49) 0.78(0.51-1.19) 1.03(0.71-1.49) 0.70(0.43-1.14)IGF1 rs5742667 1.06(0.76-1.48) 0.77(0.50-1.17) 1.04(0.71-1.51) 0.70(0.43-1.13)IGF1 rs2373721 1.06(0.77-1.48) 0.95(0.41-2.21) 0.99(0.68-1.43) 0.98(0.40-2.41)IGF1 rs7136446 1.05(0.76-1.46) 1.04(0.46-2.38) 0.98(0.68-1.41) 1.06(0.44-2.56)IGF1 rs9989002 1.00(0.71-1.39) 1.09(0.44-2.74) 0.92(0.64-1.34) 1.17(0.44-3.16)IGF1 rs5742632 1.08(0.78-1.51) 0.71(0.46-1.10) 1.04(0.71-1.51) 0.68(0.41-1.10)IGF1 rs2195240 1.08(0.78-1.50) 0.72(0.47-1.12) 1.04(0.71-1.51) 0.69(0.42-1.13)IGF1 rs5742629 1.08(0.78-1.50) 0.72(0.47-1.11) 1.04(0.72-1.51) 0.68(0.42-1.12)IGF1 rs7956547 1.05(0.75-1.48) 0.86(0.32-2.29) 0.97(0.67-1.41) 0.86(0.29-2.51)IGF1 rs4764698 0.93(0.68-1.26) 0.60(0.33-1.10) 0.88(0.62-1.24) 0.68(0.35-1.33)IGF1 rs10778176 1.08(0.78-1.51) 0.71(0.46-1.09) 1.05(0.72-1.52) 0.67(0.41-1.09)IGF1 rs2162679 0.92(0.67-1.25) 0.65(0.39-1.07) 0.76(0.54-1.09) 0.65(0.37-1.14)IGF1 rs35765 1.18(0.68-2.04) 1.04(0.56-1.94)IGF1 rs7965399 0.99(0.73-1.34) 0.74(0.39-1.37) 0.78(0.55-1.11) 0.84(0.43-1.67)IGF1 rs855211 0.98(0.72-1.34) 0.71(0.40-1.24) 0.86(0.61-1.22) 0.69(0.37-1.30)BRCA2 rs144848 1.06(0.78-1.43) 1.19(0.59-2.37) 0.96(0.68-1.36) 1.68(0.76-3.70)BRCA2 rs4942485 0.72(0.35-1.50) 0.87(0.41-1.87)IRS2 rs9515118 1.26(0.93-1.72) 0.92(0.52-1.63) 1.31(0.92-1.86) 1.02(0.55-1.90)IRS2 rs4773082 0.83(0.61-1.13) 0.72(0.38-1.38) 0.83(0.59-1.18) 0.66(0.31-1.41)IRS2 rs2289046 0.92(0.65-1.29) 1.18(0.78-1.78) 0.97(0.66-1.42) 1.10(0.69-1.75)IRS2 rs754204 0.70(0.52-0.96) 0.89(0.50-1.58) 0.73(0.52-1.03) 0.82(0.42-1.60)IRS2 rs7987237 1.24(0.91-1.70) 1.11(0.60-2.05) 1.38(0.97-1.96) 1.14(0.58-2.24)IRS2 rs12584136 0.76(0.43-1.34) 0.75(0.39-1.44)IRS2 rs9559648 0.66(0.48-0.92) 1.15(0.54-2.45) 0.66(0.46-0.95) 1.03(0.43-2.48)IRS2 rs9559654 0.79(0.57-1.10) 1.14(0.48-2.68) 0.79(0.54-1.14) 1.26(0.49-3.22)IRS2 rs7997595 1.10(0.81-1.51) 1.07(0.62-1.85) 1.11(0.78-1.59) 1.15(0.63-2.11)IRS2 rs7981705 0.67(0.33-1.35) 1.01(0.49-2.09)IRS2 rs4773092 1.05(0.74-1.49) 0.95(0.63-1.44) 1.04(0.71-1.53) 0.84(0.53-1.34)ESR2 rs1255998 1.14(0.81-1.60) 1.18(0.78-1.80) 1.12(0.77-1.64) 1.08(0.67-1.74)ESR2 rs8018687 0.91(0.61-1.38) 0.40(0.04-3.83) 0.96(0.60-1.53) 0.44(0.04-4.41)ESR2 rs928554 0.93(0.68-1.28) 1.03(0.65-1.62) 0.98(0.68-1.40) 1.13(0.67-1.89)ESR2 rs1152579 0.91(0.66-1.25) 1.02(0.65-1.60) 0.95(0.66-1.36) 1.11(0.67-1.86)ESR2 rs1256049 1.23(0.90-1.67) 1.20(0.66-2.15) 1.16(0.82-1.64) 1.02(0.52-2.00)ESR2 rs1256030 0.97(0.71-1.34) 0.99(0.63-1.55) 0.99(0.69-1.42) 1.05(0.62-1.76)ESR2 rs1271572 1.00(0.72-1.38) 0.93(0.59-1.47) 1.00(0.70-1.44) 0.98(0.58-1.66)XRCC3 rs861539 1.14(0.67-1.96) 1.14(0.61-2.13)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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XRCC3 rs1799796 0.85(0.62-1.16) 0.73(0.44-1.21) 0.78(0.55-1.10) 0.66(0.37-1.17)XRCC3 rs1799794 0.95(0.67-1.35) 0.86(0.57-1.30) 0.79(0.53-1.17) 0.78(0.49-1.23)AKT1 rs2494744 1.20(0.88-1.65) 1.14(0.71-1.82) 1.25(0.88-1.79) 1.34(0.79-2.26)AKT1 rs2498787 1.16(0.84-1.60) 1.19(0.74-1.89) 1.20(0.84-1.72) 1.44(0.86-2.42)CYP20 rs4646 0.92(0.67-1.25) 0.76(0.44-1.30) 1.09(0.77-1.55) 1.01(0.56-1.82)CYP19 rs10046 0.92(0.65-1.30) 1.00(0.66-1.52) 1.06(0.71-1.56) 1.36(0.85-2.18)CYP21 rs727479 0.83(0.61-1.13) 0.64(0.37-1.10) 0.99(0.70-1.40) 0.90(0.51-1.58)MAP2K1 rs7174378 1.03(0.73-1.45) 0.82(0.53-1.26) 0.91(0.62-1.34) 0.75(0.46-1.23)MAP2K1 rs7181936 1.12(0.81-1.54) 1.22(0.78-1.92) 1.24(0.86-1.78) 1.25(0.76-2.08)MAP2K1 rs28620576 1.07(0.79-1.46) 1.32(0.77-2.27) 1.24(0.88-1.76) 1.33(0.73-2.43)MAP2K1 rs8039880 0.91(0.65-1.26) 0.78(0.50-1.21) 0.90(0.63-1.29) 0.69(0.42-1.15)CYP1A1 rs1048943 1.48(1.09-2.03) 2.10(1.08-4.10) 1.59(1.12-2.26) 1.58(0.73-3.38)IGF1R rs4966007 1.15(0.83-1.59) 1.12(0.72-1.75) 1.41(0.98-2.03) 1.32(0.80-2.18)IGF1R rs8028620 0.97(0.69-1.37) 0.96(0.64-1.45) 1.16(0.78-1.71) 1.23(0.77-1.95)IGF1R rs4966009 1.14(0.83-1.58) 1.19(0.76-1.85) 1.41(0.98-2.04) 1.38(0.83-2.29)IGF1R rs8027457 0.98(0.70-1.39) 1.00(0.66-1.49) 1.18(0.80-1.75) 1.25(0.79-1.98)IGF1R rs4966012 0.88(0.65-1.20) 0.86(0.49-1.51) 0.94(0.66-1.32) 0.74(0.39-1.41)IGF1R rs1574213 0.89(0.65-1.22) 2.19(1.03-4.69) 0.85(0.59-1.22) 1.85(0.79-4.33)IGF1R rs11630479 0.90(0.66-1.22) 0.90(0.51-1.57) 0.97(0.68-1.36) 0.75(0.39-1.44)IGF1R rs4966013 1.21(0.85-1.72) 1.19(0.78-1.81) 1.25(0.84-1.86) 1.15(0.72-1.84)IGF1R rs4966015 0.83(0.61-1.13) 0.86(0.41-1.81) 0.90(0.64-1.28) 0.81(0.35-1.87)IGF1R rs8032477 1.13(0.79-1.61) 0.91(0.59-1.39) 1.24(0.83-1.85) 0.92(0.57-1.48)IGF1R rs11634241 0.88(0.65-1.21) 1.14(0.69-1.87) 0.91(0.64-1.29) 1.12(0.65-1.94)IGF1R rs932071 0.78(0.57-1.07) 0.95(0.48-1.86) 0.76(0.52-1.09) 0.91(0.44-1.89)IGF1R rs875686 0.84(0.62-1.15) 0.91(0.49-1.68) 0.84(0.59-1.20) 0.99(0.49-1.97)IGF1R rs1567811 0.91(0.66-1.26) 0.85(0.54-1.34) 0.92(0.64-1.33) 0.87(0.53-1.45)IGF1R rs11632952 0.85(0.62-1.17) 0.87(0.44-1.71) 0.81(0.56-1.16) 0.78(0.38-1.62)IGF1R rs4966024 0.92(0.64-1.31) 0.95(0.62-1.45) 1.05(0.70-1.57) 0.97(0.60-1.57)IGF1R rs8041224 0.84(0.60-1.16) 0.74(0.48-1.16) 0.83(0.58-1.20) 0.68(0.42-1.12)IGF1R rs7175052 0.82(0.60-1.14) 0.67(0.43-1.04) 0.87(0.61-1.25) 0.60(0.36-0.99)IGF1R rs2137680 0.98(0.69-1.40) 0.87(0.58-1.32) 1.13(0.76-1.69) 0.86(0.54-1.37)IGF1R rs12439557 0.90(0.66-1.23) 0.75(0.44-1.29) 0.95(0.67-1.35) 0.66(0.36-1.22)IGF1R rs4966028 1.01(0.72-1.43) 0.97(0.38-2.51) 1.03(0.70-1.52) 1.19(0.41-3.39)IGF1R rs907806 0.94(0.67-1.32) 1.19(0.41-3.44) 0.97(0.66-1.42) 1.64(0.48-5.62)IGF1R rs8041953 1.00(0.71-1.39) 1.08(0.41-2.85) 1.09(0.75-1.58) 1.46(0.49-4.34)IGF1R rs2670501 0.72(0.52-0.99) 0.74(0.48-1.16) 0.75(0.52-1.08) 0.66(0.40-1.10)IGF1R rs4246340 1.05(0.74-1.48) 1.44(0.94-2.21) 1.09(0.74-1.61) 1.36(0.85-2.17)IGF1R rs2684777 0.79(0.57-1.09) 1.06(0.68-1.64) 0.84(0.58-1.20) 1.07(0.65-1.75)IGF1R rs8030950 1.08(0.79-1.48) 0.99(0.52-1.85) 1.16(0.82-1.66) 0.95(0.47-1.92)IGF1R rs12594847 1.02(0.74-1.40) 1.02(0.64-1.61) 1.02(0.71-1.45) 0.94(0.56-1.57)IGF1R rs2684781 0.95(0.69-1.31) 0.92(0.58-1.43) 0.99(0.69-1.42) 0.86(0.52-1.43)IGF1R rs1521481 1.02(0.75-1.40) 0.99(0.55-1.80) 1.10(0.77-1.56) 0.84(0.42-1.67)IGF1R rs4966035 0.68(0.48-0.96) 0.99(0.66-1.48) 0.64(0.44-0.95) 0.96(0.61-1.52)IGF1R rs4966036 0.82(0.60-1.13) 1.01(0.65-1.58) 0.86(0.60-1.23) 1.15(0.70-1.90)IGF1R rs7165875 0.74(0.52-1.05) 1.06(0.71-1.58) 0.67(0.45-0.99) 1.02(0.65-1.61)IGF1R rs3743259 0.68(0.48-0.96) 1.04(0.69-1.57) 0.62(0.42-0.92) 1.03(0.65-1.63)IGF1R rs3743260 1.16(0.82-1.64) 0.68(0.25-1.87) 1.10(0.74-1.61) 0.49(0.15-1.64)IGF1R rs2684810 1.18(0.86-1.61) 1.11(0.64-1.91) 1.11(0.78-1.57) 0.97(0.52-1.79)IGF1R rs4966039 0.94(0.68-1.30) 0.67(0.28-1.63) 0.92(0.65-1.32) 0.57(0.21-1.55)IGF1R rs2684805 1.07(0.77-1.50) 0.95(0.61-1.47) 1.22(0.84-1.77) 1.03(0.63-1.68)IGF1R rs2684803 1.29(0.95-1.77) 0.99(0.61-1.62) 1.38(0.97-1.97) 1.18(0.70-2.00)IGF1R rs1546713 1.28(0.94-1.75) 0.99(0.61-1.61) 1.37(0.96-1.95) 1.17(0.69-1.98)IGF1R rs7166558 1.28(0.93-1.75) 1.02(0.63-1.66) 1.37(0.96-1.95) 1.22(0.72-2.06)IGF1R rs2229765 1.27(0.93-1.74) 1.00(0.61-1.64) 1.35(0.95-1.92) 1.20(0.71-2.03)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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IGF1R rs11635251 1.08(0.80-1.48) 0.73(0.43-1.24) 1.10(0.78-1.56) 0.66(0.37-1.19)IGF1R rs8038056 1.42(1.04-1.93) 0.40(0.21-0.76) 1.34(0.95-1.90) 0.37(0.17-0.77)IGF1R rs12916884 1.16(0.85-1.58) 0.60(0.36-1.00) 1.16(0.81-1.64) 0.63(0.36-1.11)IGF1R rs7173377 1.33(0.97-1.82) 0.84(0.51-1.39) 1.25(0.88-1.77) 0.74(0.41-1.33)IGF1R rs7166565 1.39(1.02-1.91) 0.86(0.52-1.42) 1.29(0.91-1.83) 0.74(0.41-1.32)IGF1R rs939626 1.08(0.79-1.47) 0.51(0.26-0.98) 0.92(0.64-1.32) 0.55(0.26-1.13)IGF1R rs12437963 1.01(0.73-1.39) 1.10(0.70-1.73) 0.98(0.68-1.40) 1.13(0.69-1.86)IGF1R rs2684788 0.90(0.64-1.26) 0.94(0.62-1.43) 0.88(0.60-1.29) 0.99(0.63-1.58)IGF1R rs1815009 0.96(0.69-1.35) 0.90(0.60-1.37) 0.93(0.64-1.37) 0.95(0.60-1.49)A2BP1 rs7203563 0.81(0.59-1.12) 0.89(0.40-2.00) 0.81(0.56-1.16) 1.03(0.41-2.57)TNRC9/LOC643714 rs8051542 0.98(0.71-1.34) 1.58(0.77-3.26) 1.01(0.71-1.44) 1.37(0.62-3.03)TNRC9/LOC643714 rs12443621 0.93(0.68-1.28) 1.12(0.70-1.79) 0.89(0.63-1.27) 0.95(0.56-1.60)TNRC9 or TOX3 rs3803662 0.93(0.68-1.29) 0.80(0.51-1.27) 0.97(0.68-1.39) 0.90(0.54-1.51)ATP1B2 rs1641512 0.93(0.67-1.27) 0.74(0.47-1.16) 0.94(0.66-1.35) 0.76(0.46-1.27)TP53 rs9894946 1.03(0.57-1.85) 0.84(0.43-1.65)TP53 rs1614984 0.75(0.55-1.03) 0.65(0.39-1.07) 0.76(0.53-1.08) 0.73(0.41-1.31)TP53 rs1042522 0.69(0.50-0.95) 0.68(0.43-1.08) 0.63(0.44-0.90) 0.81(0.48-1.37)WDR79 rs2287499 0.66(0.49-0.91) 0.63(0.31-1.30) 0.66(0.47-0.94) 0.61(0.26-1.44)WDR79 rs17885803 0.83(0.55-1.24) 0.59(0.05-6.50) 0.79(0.50-1.25) 0.58(0.05-6.88)WDR79 rs2287498 0.66(0.49-0.91) 0.64(0.31-1.31) 0.67(0.47-0.95) 0.62(0.26-1.45)HER2 rs1565923 1.06(0.76-1.47) 1.27(0.82-1.99) 0.92(0.64-1.32) 0.99(0.60-1.63)ERBB rs1810132 1.05(0.76-1.46) 1.25(0.80-1.95) 0.91(0.63-1.31) 0.98(0.60-1.63)HER2 rs3809717 1.01(0.74-1.37) 1.19(0.67-2.09) 0.93(0.66-1.32) 0.87(0.46-1.64)ITGB3 rs3809865 0.88(0.64-1.22) 1.25(0.62-2.54) 1.08(0.76-1.54) 1.34(0.62-2.90)ITGA3 rs1062484 0.73(0.17-3.06) 0.69(0.12-3.93)AXIN2 rs7210356 1.15(0.81-1.64) 0.52(0.18-1.49) 0.92(0.62-1.38) 0.59(0.19-1.82)AXIN2 rs4791171 0.87(0.63-1.19) 0.82(0.52-1.31) 0.82(0.58-1.18) 0.70(0.41-1.18)AXIN2 rs11079571 1.13(0.82-1.54) 1.39(0.82-2.39) 1.01(0.71-1.43) 1.46(0.78-2.74)AXIN2 rs3923087 0.84(0.61-1.15) 1.01(0.63-1.61) 0.79(0.55-1.13) 0.87(0.52-1.47)AXIN2 rs3923086 0.97(0.70-1.35) 0.96(0.37-2.47) 0.94(0.65-1.36) 0.60(0.19-1.88)GPX4 rs4807542 0.88(0.63-1.22) 0.73(0.35-1.54) 0.99(0.69-1.43) 0.65(0.25-1.65)MAP2K2 rs350916 1.29(0.94-1.78) 1.30(0.82-2.08) 1.34(0.94-1.92) 1.10(0.65-1.84)MAP2K2 rs350913 1.41(1.02-1.94) 1.25(0.79-1.98) 1.50(1.05-2.16) 1.09(0.65-1.81)MAP2K2 rs7258366 1.60(1.17-2.18) 1.51(0.91-2.50) 1.62(1.14-2.30) 1.15(0.65-2.02)MAP2K2 rs350894 1.37(0.98-1.90) 1.33(0.85-2.10) 1.43(0.99-2.06) 1.18(0.71-1.95)MAP2K2 rs12459484 1.76(1.27-2.45) 1.87(1.21-2.91) 1.80(1.25-2.61) 1.54(0.93-2.53)ICAM5 rs1056538 1.08(0.79-1.48) 1.21(0.72-2.03) 0.99(0.69-1.40) 1.11(0.63-1.95)CCNE1 rs997669 1.32(0.89-1.96) 1.27(0.32-5.14) 1.47(0.95-2.29) 1.25(0.24-6.47)XRCC1 rs25487 1.42(1.04-1.92) 1.25(0.61-2.57) 1.58(1.12-2.23) 1.07(0.46-2.49)PTGIS rs6095541 0.82(0.54-1.25) 1.18(0.07-18.94) 0.61(0.36-1.02) 0.91(0.06-14.8)PTGIS rs6095543 1.01(0.72-1.40) 0.48(0.15-1.55) 0.91(0.62-1.32) 0.49(0.13-1.93)PTGIS rs693649 1.08(0.78-1.49) 0.88(0.56-1.38) 1.11(0.78-1.60) 1.04(0.63-1.74)AURKA rs8173 1.11(0.82-1.52) 1.39(0.83-2.31) 1.08(0.76-1.53) 1.16(0.66-2.06)AURKA rs10485805 0.97(0.71-1.32) 1.73(0.87-3.46) 0.97(0.68-1.37) 1.30(0.58-2.88)AURKA rs6024840 1.11(0.81-1.52) 0.87(0.52-1.46) 1.10(0.78-1.56) 0.76(0.43-1.37)AURKA rs911160 1.10(0.81-1.51) 0.90(0.54-1.50) 1.10(0.78-1.57) 0.75(0.42-1.34)AURKA rs2298016 1.02(0.74-1.39) 0.88(0.54-1.43) 1.01(0.71-1.44) 0.73(0.41-1.27)AURKA rs2273535 1.02(0.75-1.40) 0.87(0.54-1.42) 1.00(0.70-1.43) 0.71(0.41-1.25)COMT rs4680 0.68(0.50-0.93) 1.17(0.65-2.08) 0.66(0.46-0.93) 1.16(0.61-2.21)CHEK2 rs9608698 0.83(0.61-1.13) 1.99(0.97-4.05) 0.83(0.58-1.17) 2.14(1.02-4.49)AR rs2361634 1.22(0.08-19.51)PHKA1 rs3012642 1.01(0.72-1.42) 1.61(0.69-3.74) 　 1.07(0.74-1.55) 1.29(0.53-3.15)OR(95%CI)1:Univariate logistic regression model. OR(95%CI)2:Multivariate logistic regression model. Adjusted for age at diagnosis, BMI, age at menarche, and age at first parturition.

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Gene p-value Number of SNPsIGF1R 0.000320067 51MAP2K2 0.001311089 5ECHDC1 0.001953968 4MAP2K1 0.024404878 4CCND1 0.050450431 2GATA3 0.096671624 2ABCB1 0.100887769 11XRCC3 0.172878514 3AURKA 0.191339271 5ESR1 0.197256908 23AKT1 0.246848403 4IGF1 0.282926676 8WDR79 0.339101908 3TNRC9/LOC643714 0.41130922 2ESR2 0.41547396 6BARD1 0.419480651 7PTGIS 0.432614379 3CDKN1A 0.476171209 2STE or SULT1E1 0.480890399 2IGF1 0.507752199 13LSP1 0.609700011 2CYP1B1 0.620762209 2PGR 0.625302692 7KIT 0.642231988 11ESR1 0.777452327 5KDR 0.834710915 8AXIN2 0.840085478 5IRS2 0.90313887 11FGFR1 0.903297222 6FGFR2 0.914000496 10HSD11B1 0.915633612 5HER2 0.917903667 2EGFR 0.927950541 10APC 0.989573417 10MET 0.999908114 11

Table 11. Gene-based analyses: global p-values for significant associations between breast cancer and common genetic variation

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FIGURE 5-1. Schematic diagrams of the

location of the SNPs in HSD11B1 , and

strength of the LD between SNPs.


location of the SNPs in IGF1 , and strength

of the LD between SNPs.

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location of the SNPs in ESR2 , and strength

of the LD between SNPs.


location of the SNPs in IGF1R , and

strength of the LD between SNPs.

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IGF1 control TN 　　

　 N (%) N (%) OR(95%CI)1 OR(95%CI)2

haplotype ht1

ㅡ/ㅡ 242(61.7) 195(59.5) 1 (ref) 1 (ref)

ㅡ/ht1 125(31.9) 112(34.2) 1.11(0.81-1.53) 1.24(0.73-2.09)

ht1/ht1 25(6.4) 21(6.4) 1.04(0.57-1.92) 2.80(0.66-11.86)

p for linear trend 0.6145 0.1727

haplotype ht2

ㅡ/ㅡ 255(65.1) 208(63.4) 1 (ref) 1 (ref)

ㅡ/ht2 121(30.9) 100(30.5) 1.01(0.73-1.40) 0.99(0.57-1.71)

ht2/ht2 16(4.1) 20(6.1) 1.53(0.77-3.03) 1.03(0.26-4.12)


haplotype ht3

ㅡ/ㅡ 249(63.5) 214(65.2) 1 (ref) 1 (ref)

ㅡ/ht3 122(31.1) 102(31.1) 0.97(0.71-1.34) 1.11(0.64-1.92)

ht3/ht3 21(5.4) 12(3.7) 0.67(0.32-1.38) 0.24(0.03-2.05)


haplotype ht4

ㅡ/ㅡ 287(73.2) 244(74.4) 1 (ref) 1 (ref)

ㅡ/ht4 96(24.5) 77(23.5) 0.94(0.67-1.33) 0.75(0.41-1.36)

ht4/ht4 9(2.3) 7(2.1) 0.92(0.34-2.49) 1.09(0.21-5.63)

p for linear trend 　　 0.7202 0.4842

OR(95%CI)1:Univariate logistic regression model.

OR(95%CI)2:Multivariate logistic regression model .Adjusted age at diganosis, BMI, age at menarche, age at

post-menopausal.

Table 12-1. Association between haplotypes and triple negative breast cancer risk

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IRS2 control TN 　　

　 N (%) N (%) OR(95%CI)1 OR(95%CI)2

haplotype ht1

ㅡ/ㅡ 166(42.4) 127(38.7) 1 (ref) 1 (ref)

ㅡ/ht1 179(45.7) 164(50.0) 1.20(0.88-1.64) 1.37(0.79-2.36)

ht1/ht1 47(12.0) 37(11.3) 1.03(0.63-1.68) 2.48(1.08-5.70)


haplotype ht2

ㅡ/ㅡ 248(63.3) 199(60.7) 1 (ref) 1 (ref)

ㅡ/ht2 126(32.1) 113(34.5) 1.12(0.82-1.53) 1.11(0.64-1.92)

ht2/ht2 18(4.6) 16(4.9) 1.11(0.55-2.23) 0.64(0.19-2.20)


haplotype ht3

ㅡ/ㅡ 270(68.9) 238(72.6) 1 (ref) 1 (ref)

ㅡ/ht3 115(29.3) 81(24.7) 0.80(0.57-1.12) 0.70(0.39-1.24)

ht3/ht3 7(1.8) 9(2.7) 1.46(0.54-3.98) 1.35(0.18-10.24)


haplotype ht4

ㅡ/ㅡ 342(87.2) 283(86.3) 1 (ref) 1 (ref)

ㅡ/ht4 47(12.0) 43(13.1) 1.11(0.71-1.72) 1.71(0.77-3.80)

ht4/ht4 3(0.8) 2(0.6) 0.81(0.13-4.86)

p for linear trend 　　 0.7669 0.3456

OR(95%CI)1: Univariate logistic regression model

OR(95%CI)2: Multivariate logistic regression model. Adjusted for age at diganosis, BMI, age at menarche, age at

post-menopausal.


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IGF1R_block1 control TN 　　

　 N (%) N (%) OR(95%CI)1

OR(95%CI)2

haplotype ht1

ㅡ/ㅡ 161(41.1) 124(37.8) 1 (ref) 1 (ref)

ㅡ/ht1 174(44.4) 155(47.3) 1.16(0.84-1.59) 1.45(0.82-2.53)

ht1/ht1 57(14.5) 49(14.9) 1.12(0.71-1.75) 1.37(0.62-3.03)

pforlineartrend 0.4802 0.2803

haplotype ht2

ㅡ/ㅡ 189(48.2) 161(49.1) 1 (ref) 1 (ref)

ㅡ/ht2 166(42.4) 132(40.2) 0.93(0.68-1.27) 0.83(0.49-1.41)

ht2/ht2 37(9.4) 35(10.7) 1.11(0.67-1.85) 0.66(0.22-1.98)


haplotype ht3

ㅡ/ㅡ 245(62.5) 208(63.4) 1 (ref) 1 (ref)

ㅡ/ht3 137(35.0) 100(30.5) 0.86(0.63-1.18) 0.76(0.43-1.33)

ht3/ht3 10(2.6) 20(6.1) 2.36(1.08-5.15) 2.07(0.69-6.22)


haplotype ht4

ㅡ/ㅡ 335(85.5) 293(89.3) 1 (ref) 1 (ref)

ㅡ/ht4 53(13.5) 33(10.1) 0.71(0.45-1.13) 0.65(0.30-1.40)

ht4/ht4 4(1.0) 2(0.6) 0.57(0.10-3.14) 1.41(0.08-24.63)

pforlineartrend 　　　0.1204 0.3769　OR(95%CI)1:Univariate logistic regression model.

OR(95%CI)2:Multivariate logistic regression model. Adjusted age at diganosis, BMI, age at menarche, age at post-menopausal


- 74 -


　 N (%) N (%) OR(95%CI)1 OR(95%CI)2

haplotype ht1

ㅡ/ㅡ 256(65.3) 201(61.3) 1 (ref) 1 (ref)

ㅡ/ht1 119(30.4) 113(34.5) 1.21(0.88-1.66) 1.45(0.84-2.51)

ht1/ht1 17(4.3) 14(4.3) 1.05(0.51-2.18) 0.88(0.27-2.88)


haplotype ht2

ㅡ/ㅡ 266(67.9) 229(69.8) 1 (ref) 1 (ref)

ㅡ/ht2 116(29.6) 91(27.7) 0.91(0.66-1.26) 0.70(0.40-1.23)

ht2/ht2 10(2.6) 8(2.4) 0.93(0.36-2.39) 0.60(0.17-2.08)


haplotype ht3

ㅡ/ㅡ 316(80.6) 263(80.2) 1 (ref) 1 (ref)

ㅡ/ht3 72(18.4) 60(18.3) 1.00(0.69-1.46) 1.21(0.60-2.44)

ht3/ht3 4(1.0) 5(1.5) 1.50(0.40-5.65)


haplotype ht4

ㅡ/ㅡ 333(85.0) 268(81.7) 1 (ref) 1 (ref)

ㅡ/ht4 55(14.0) 55(16.8) 1.24(0.83-1.87) 1.47(0.73-2.97)

ht4/ht4 4(1.0) 5(1.5) 1.55(0.41-5.84) 3.42(0.30-39.16)


haplotype ht5

ㅡ/ㅡ 323(82.4) 283(86.3) 1 (ref) 1 (ref)

ㅡ/ht5 64(16.3) 43(13.1) 0.77(0.51-1.17) 1.04(0.51-2.11)

ht5/ht5 5(1.3) 2(0.6) 0.46(0.09-2.37) 0.45(0.05-4.50)


haplotype ht6

ㅡ/ㅡ 336(85.7) 283(86.3) 1 (ref) 1 (ref)

ㅡ/ht6 56(14.3) 44(13.4) 0.93(0.61-1.43) 0.79(0.37-1.68)

ht6/ht6 0(0.0) 1(0.3)

pforlineartrend 　　　0.9212 　0.537 　


OR(95%CI)2:Multivariate logistic regression model. Adjusted age at diganosis, BMI, age at menarche, age at post-menopausal


- 75 -


　 N (%) N (%) OR(95%CI)1 OR(95%CI)2

haplotype ht1

ㅡ/ㅡ 125(31.9) 96(29.3) 1 (ref) 1 (ref)

ㅡ/ht1 205(52.3) 163(49.7) 1.04(0.74-1.45) 1.14(0.62-2.09)

ht1/ht1 62(15.8) 69(21.0) 1.45(0.94-2.24) 1.80(0.88-3.68)


haplotype ht2

ㅡ/ㅡ 143(36.5) 147(44.8) 1 (ref) 1 (ref)

ㅡ/ht2 190(48.5) 136(41.5) 0.70(0.51-0.96) 0.44(0.25-0.79)

ht2/ht2 59(15.1) 45(13.7) 0.74(0.47-1.17) 0.71(0.34-1.46)


haplotype ht3

ㅡ/ㅡ 292(74.5) 247(75.3) 1 (ref) 1 (ref)

ㅡ/ht3 93(23.7) 76(23.2) 0.97(0.68-1.37) 1.06(0.57-1.97)

ht3/ht3 7(1.8) 5(1.5) 0.84(0.27-2.69) 2.13(0.19-24.49)

pforlineartrend 　　 0.7644　 0.6625　


OR(95%CI)2:Multivariate logistic regression model. Adjusted age at diganosis, BMI, age at menarche, age at

post-menopausal


- 76 -


　 N (%) N (%) OR(95%CI)1 OR(95%CI)2

haplotype ht1

ㅡ/ㅡ 168(42.9) 150(45.7) 1 (ref) 1 (ref)

ㅡ/ht1 191(48.7) 136(41.5) 0.80(0.58-1.09) 0.53(0.30-0.92)

ht1/ht1 33(8.4) 42(12.8) 1.43(0.86-2.37) 1.48(0.64-3.41)


haplotype ht2

ㅡ/ㅡ 269(68.6) 215(65.6) 1 (ref) 1 (ref)

ㅡ/ht2 107(27.3) 100(30.5) 1.17(0.84-1.62) 1.09(0.62-1.92)

ht2/ht2 16(4.1) 13(4.0) 1.02(0.48-2.16) 0.74(0.17-3.23)


haplotype ht3

ㅡ/ㅡ 260(66.3) 233(71.0) 1 (ref) 1 (ref)

ㅡ/ht3 124(31.6) 82(25.0) 0.74(0.53-1.03) 0.60(0.33-1.08)

ht3/ht3 8(2.0) 13(4.0) 1.81(0.74-4.45) 3.80(0.76-19.02)


haplotype ht4

ㅡ/ㅡ 332(84.7) 269(82.0) 1 (ref) 1 (ref)

ㅡ/ht4 54(13.8) 54(16.5) 1.23(0.82-1.86) 1.39(0.67-2.89)

ht4/ht4 6(1.5) 5(1.5) 1.03(0.31-3.41) 5.01(0.53-47.67)

pforlineartrend 　　　0.398 　0.1168


OR(95%CI)2:Multivariate logistic regression model. Adjusted age at diganosis, BMI, age at menarche, age at

post-menopausal.


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Table 13. Baseline patient and tumor characteristics.Characteristics overall

(n=190)recur

(n=30)non-recur

(n=160)Age at diagnosis, median (range), y 45(65) 45(37) 45(65)Age at menarche, median (range), y 15(10) 15(9) 15(10)Age at first parturition, median (range), y

26(30) 26(25) 26(18)BMI,kg/m2 22(16) 22(10) 23(16)

Follow-up, median (range), mo 47(90) 27(62) 52(87)Tumor size, cm, No (%)

≤ 2 101(53.2) 15(50.0) 86(53.8)> 2 85(44.7) 13(43.3) 72(45.0)unknown 4(2.1) 2(6.7) 2(1.2)

Node status, No (%)N0 122(64.6) 17(58.6) 105(65.6)N1 53(28.0) 8(27.6) 45(28.1)N2 + N3 14(7.4) 4(13.8) 10(6.3)

Stage, No (%)0 3(1.6) 0(0) 3(1.9)1 62(33.2) 8(28.6) 54(34.0)2 96(51.3) 15(53.6) 81(50.9)3 23(12.3) 5(17.9) 18(11.3)unknown 3(1.6) 　 0(0) 　 3(1.9)

Nuclear grade, No (%)low 3(2.0) 1(4.2) 2(1.6)intermediate 36(24.3) 8(33.3) 28(22.6)high 109(73.7) 15(62.5) 94(75.8)

p53, No (%)negative 58(33.9) 5(19.2) 53(36.6)weak 22(12.9) 3(11.5) 19(13.1)intermediate 20(11.7) 4(15.4) 16(11.0)strong 71(41.5) 14(53.9) 57(39.3)

2) 삼중음성유방암 환자군에서 재발과 관련된 SNP 연구

(1) 연구대상자

¡ 2003년부터 2007년까지 유방암으로 진단받고 수술/치료를 받은 환자 중 조직학적으로 확진되고 IHC가 판독 가능하면서 DNA가 유용한 여성 유방암 환자 190명 중에서 재발군(30명)과 비재발군(160명)을 대상으로 함

- 78 -

Figure 6-1.

- 79 -

Figure 6-2.

- 80 -

Figure 6-3.

- 81 -

Figure 6-4.

- 82 -

Figure 6-5.

- 83 -

Figure 6-6.

- 84 -

Table 14 . Cox Proportional Hazard Models for several SNPs

Gene Genotyperecur non-recur

HazardRatio1 　HazardRatio2 　

HazardRatio3 　HazardRatio4

N (%) 　　　

2p(19150424) GG 4(13.3) 9(5.6) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 26(86.7) 151(94.4) 2.74(0.95-7.87) 2.59(0.54-12.51) 2.74(0.74-10.21) 2.58(0.66-10.06)

BARD1 CC 7(23.3) 71(44.4) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AC 17(56.7) 78(48.8) 2.16(0.90-5.21) 1.70(0.63-4.55) 3.70(1.21-11.27) 2.89(0.92-9.12)

AA 6(20.0) 11(6.9) 5.13(1.72-15.30) 3.73(1.02-13.60) 7.44(1.97-28.14) 11.21(2.54-49.36)

BARD1 GG 7(23.3) 84(52.8) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CG 18(60.0) 64(40.3) 3.35(1.40-8.03) 2.74(1.03-7.28) 5.67(1.91-16.87) 4.67(1.56-13.99)

CC 5(16.7) 11(6.9) 5.40(1.71-17.03) 3.65(0.88-15.22) 7.08(1.78-28.15) 9.36(2.13-41.15)

FGFR2 TT 4(13.3) 43(26.9) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CT 17(56.7) 95(59.4) 1.82(0.61-5.42) 6.85(0.89-52.86) 1.63(0.51-5.17) 2.26(0.62-8.30)

CC 9(30.0) 22(13.8) 3.74(1.15-12.15) 18.43(2.25-150.75) 2.59(0.73-9.24) 3.95(0.94-16.51)

KIT AA 12(40.0) 94(58.8) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 13(43.3) 60(37.5) 1.87(0.85-4.10) 1.58(0.64-3.87) 1.52(0.62-3.73) 1.25(0.50-3.14)

GG 5(16.7) 6(3.8) 4.15(1.46-11.77) 2.27(0.50-10.42) 3.82(1.03-14.21) 2.72(0.70-10.58)

KDR AA 12(40.0) 81(50.6) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 18(60.0) 65(40.6) 1.79(0.86-3.72) 1.97(0.83-4.67) 1.96(0.84-4.57) 1.56(0.65-3.74)

GG 0(0.0) 14(8.8)

LSP1 GG 6(20.0) 59(36.9) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 17(56.7) 80(50.0) 2.09(0.82-5.29) 3.05(0.84-11.02) 2.30(0.78-6.75) 2.75(0.81-9.36)

AA 7(23.3) 21(13.1) 3.16(1.06-9.43) 7.99(1.91-33.38) 3.19(0.89-11.46) 4.06(1.05-15.73)

ESR1 CC 22(73.3) 119(74.4) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CT 6(20.0) 40(25.0) 0.77(0.31-1.89) 0.86(0.30-2.43) 0.39(0.11-1.40) 0.49(0.14-1.71)

TT 2(6.7) 1(0.6) 4.82(1.13-20.52) 3.27(0.63-17.00) 3.07(0.37-25.51) 1.99(0.23-17.38)

ESR1 TT 22(73.3) 118(73.8) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CT 6(20.0) 41(25.6) 0.74(0.30-1.82) 0.80(0.28-2.29) 0.37(0.10-1.32) 0.46(0.13-1.63)

CC 2(6.7) 1(0.6) 4.77(1.12-20.31) 3.16(0.60-16.62) 2.96(0.36-24.71) 1.96(0.22-17.12)

ESR1 CC 9(30.0) 60(37.5) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AC 13(43.3) 82(51.3) 1.19(0.51-2.77) 1.76(0.63-4.86) 1.17(0.43-3.22) 1.32(0.46-3.74)

AA 8(26.7) 18(11.3) 3.04(1.17-7.91) 3.55(1.04-12.10) 3.25(1.05-10.10) 3.45(1.09-10.90)

ESR1 GG 10(33.3) 73(45.6) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

GT 12(40.0) 76(47.5) 1.22(0.53-2.82) 1.53(0.58-4.09) 1.42(0.51-3.93) 1.59(0.56-4.52)

TT 8(26.7) 11(6.9) 3.98(1.57-10.10) 4.05(1.25-13.13) 5.21(1.67-16.25) 5.72(1.81-18.12)

ABCB1 GG 15(50.0) 49(30.6) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 13(43.3) 82(51.3) 0.54(0.26-1.14) 0.51(0.21-1.25) 0.56(0.24-1.29) 0.57(0.24-1.36)

AA 2(6.7) 29(18.1) 0.25(0.06-1.09) 0.36(0.08-1.65) 0.19(0.02-1.51) 0.25(0.03-2.06)

Q129R GG 8(26.7) 79(49.4) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 19(63.3) 68(42.5) 2.68(1.17-6.12) 3.04(1.06-8.71) 1.88(0.74-4.81) 1.86(0.71-4.86)

AA 3(10.0) 13(8.1) 1.72(0.46-6.48) 4.25(0.95-18.95) 1.02(0.22-4.74) 1.43(0.32-6.46)

H19 CC 17(56.7) 47(29.4) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CT 9(30.0) 80(50.0) 0.32(0.14-0.73) 0.43(0.17-1.12) 0.25(0.10-0.66) 0.27(0.10-0.73)

TT 4(13.3) 33(20.6) 0.38(0.13-1.14) 0.51(0.14-1.82) 0.37(0.10-1.37) 0.45(0.12-1.69)

IGF1 GG 29(96.7) 158(99.4) 1 (ref) 1 (ref) 1 (ref)

GT 1(3.3) 1(0.6) 10.76(1.37-84.5) 9.85(1.08-89.93) 12.76(1.35-120.7)

IRS2 AA 4(14.3) 50(31.3) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 14(50.0) 76(47.5) 2.35(0.77-7.13) 4.52(1.00-20.44) 1.60(0.48-5.29) 1.97(0.58-6.74)

GG 10(35.7) 34(21.3) 3.50(1.10-11.18) 4.38(0.88-21.75) 1.75(0.45-6.75) 1.56(0.41-5.93)

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CYP19A1 CC 11(36.7) 92(57.9) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AC 17(56.7) 54(34.0) 2.66(1.25-5.69) 2.63(1.06-6.56) 3.10(1.19-8.09) 2.93(1.11-7.76)

AA 2(6.7) 13(8.2) 1.06(0.23-4.78) 0.54(0.07-4.53) 1.54(0.31-7.66) 1.30(0.26-6.59)

CYP19A1 TT 10(33.3) 92(57.5) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

GT 16(53.3) 56(35.0) 2.75(1.25-6.08) 2.98(1.11-7.98) 3.82(1.43-10.21) 3.29(1.21-8.93)

GG 4(13.3) 12(7.5) 2.51(0.79-8.00) 2.12(0.51-8.80) 4.58(1.00-21.07) 3.01(0.66-13.67)

IGF1R CC 16(53.3) 65(40.6) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AC 14(46.7) 72(45.0) 0.80(0.39-1.65) 0.80(0.33-1.91) 0.98(0.42-2.31) 0.80(0.34-1.91)

AA 0(0.0) 23(14.4)

IGF1R TT 20(66.7) 76(47.5) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CT 7(23.3) 71(44.4) 0.39(0.17-0.93) 0.38(0.14-0.99) 0.41(0.14-1.18) 0.33(0.12-0.95)

CC 3(10.0) 13(8.1) 0.81(0.24-2.74) 0.44(0.06-3.42) 0.95(0.21-4.32) 0.87(0.19-4.04)

IGF1R AA 16(53.3) 62(38.8) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 11(36.7) 90(56.3) 0.47(0.22-1.02) 0.50(0.20-1.24) 0.51(0.21-1.23) 0.50(0.20-1.28)

GG 3(10.0) 8(5.0) 1.81(0.53-6.23) 2.57(0.53-12.42) 2.34(0.56-9.72) 2.67(0.64-11.26)

IGF1R AA 7(23.3) 72(45.0) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 19(63.3) 62(38.8) 2.91(1.22-6.94) 2.07(0.78-5.51) 2.04(0.75-5.53) 1.81(0.63-5.25)

GG 4(13.3) 26(16.3) 1.64(0.48-5.62) 1.37(0.33-5.68) 0.76(0.19-3.07) 0.73(0.17-3.19)

IGF1R GG 9(30.0) 55(34.4) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 19(63.3) 66(41.3) 1.59(0.72-3.52) 1.25(0.50-3.13) 1.32(0.51-3.45) 1.54(0.55-4.29)

AA 2(6.7) 39(24.4) 0.32(0.07-1.48) 0.12(0.02-0.99) 0.16(0.02-1.26) 0.15(0.02-1.21)

TP53 GG 18(60.0) 73(45.6) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CG 5(16.7) 73(45.6) 0.34(0.13-0.92) 0.28(0.08-1.03) 0.46(0.16-1.33) 0.63(0.21-1.88)

CC 7(23.3) 14(8.8) 1.65(0.69-3.96) 2.87(1.06-7.80) 1.12(0.38-3.31) 1.67(0.53-5.29)

AXIN2 GG 26(86.7) 109(68.1) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 3(10.0) 48(30.0) 0.28(0.09-0.92) 0.27(0.06-1.19) 0.10(0.01-0.77) 0.11(0.02-0.85)

AA 1(3.3) 3(1.9) 1.49(0.20-10.97) 1.01(0.11-9.16) 1.23(0.14-10.56) 2.63(0.27-25.26)

AXIN2 AA 17(56.7) 71(44.4) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 7(23.3) 73(45.6) 0.44(0.18-1.05) 0.77(0.29-2.04) 0.37(0.13-1.08) 0.35(0.12-1.04)

GG 6(20.0) 16(10.0) 1.31(0.52-3.33) 1.78(0.55-5.77) 1.49(0.50-4.43) 1.23(0.37-4.11)

AXIN2 AA 17(56.7) 69(43.1) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 6(20.0) 75(46.9) 0.35(0.14-0.88) 0.60(0.22-1.66) 0.25(0.08-0.84) 0.23(0.07-0.81)

GG 7(23.3) 16(10.0) 1.47(0.61-3.53) 2.00(0.68-5.87) 1.74(0.63-4.86) 1.54(0.51-4.70)

MAP2K2 TT 7(23.3) 64(40.0) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CT 20(66.7) 76(47.5) 2.48(1.05-5.88) 3.33(1.11-10.00) 2.45(0.90-6.62) 2.94(1.02-8.49)

CC 3(10.0) 20(12.5) 1.40(0.36-5.40) 1.82(0.32-10.27) 2.03(0.49-8.46) 2.52(0.56-11.45)

COMT GG 21(70.0) 78(48.8) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

AG 8(26.7) 65(40.6) 0.50(0.22-1.12) 0.55(0.21-1.41) 0.47(0.19-1.17) 0.54(0.21-1.37)

AA 1(3.3) 17(10.6) 0.24(0.03-1.75) 0.33(0.04-2.54) 0.39(0.05-3.10)

CHEK2 GG 24(80.0) 91(56.9) 1 (ref) 1 (ref) 1 (ref) 1 (ref)

CG 5(16.7) 59(36.9) 0.35(0.13-0.93) 0.32(0.11-0.98) 0.26(0.07-0.93) 0.28(0.08-1.03)

　 CC 1(3.3) 10(6.3) 0.52(0.07-3.83) 　　　 0.24(0.02-2.41) 　 0.31(0.04-2.76)

HazardRatio1:ProportionalHazardsRegression.

HazardRatio2:ProportionalHazardsRegressionadjustedageatdiagnosis,BMI,ageatmenarche,ageatfirst

parturition.

HazardRatio3:ProportionalHazardsRegressionadjustedageatdiagnosis,tumorsize,nodestatus,stage,nu

cleargrade.

HazardRatio4:ProportionalHazardsRegressionadjustedageatdiagnosis,tumorsize,nodestatus,stage,nucleargrade,p53mutation.

- 86 -

Characteristics Normal Case p1

Age at diagnosis (y), mean±SD 47.0 ± 9.42 56.5 ± 10.3 <.0001

< 40 , n(%) 109(27) 28(7)

40-50 143(36) 62(15)

≥50 148(37) 328(78)

Age at menarche (y), mean±SD 14.7 ± 1.65 15.9 ± 1.83 <.0001

< 14 , n(%) 159(40) 121(29)

14-15 143(36) 119(28)

> 15 98(25) 178(43) <.0001

Age at first parturition (y), mean±SD 26.8 ± 3.13 25.7 ± 4.04 0.0003

< 25 , n(%) 166(42) 221(53)

25-30 194(49) 149(36)

≥30 40(10) 48(11) 0.0009

Parity

0 , n(%) 10(5) 6(2)

1 39(19) 37(11)

2 113(54) 140(41)

≥3 46(22) 158(46) <.0001

Menopausal status

Premenopausal 298(75) 124(30)

Postmenopausal 102(26) 294(70) <.0001

Tumor size (cm), mean±SD 2.05 ± 1.30

≤2,n(%) 241(58)

> 2 177(42)

Node status, n(%)

N0 228(55)

N1 111(27)

N2+N3 78(19) 　1 t-TEST for contiunous variable and χ2 for categorical variable.

3) Aromatase inhibitor 치료 반응과 관련된 역학적 특성 연구

(1) Aromatase inhibitor 치료군과 정상 대조군간의 역학적 특성 연구

Table 15 . Baseline patient characteristics

- 87 -

　 Crude OR (95% CI) Multivariate OR (95% CI)

Age at diagnosis (y)

< 40 1 (ref.) 1 (ref.)

40-50 1.69(1.01-2.81) 1.10(0.53-2.30)

≥50 8.63(5.46-13.6) 2.00(0.93-4.32)

p for linear trend <.0001 0.0446

Age at menarche (y)

< 14 1 (ref.) 1 (ref.)

14-15 1.09(0.78-1.54) 1.79(1.05-3.06)

> 15 2.39(1.70-3.36) 2.15(1.25-3.71)


Age at first parturition

< 25 1 (ref.) 1 (ref.)

25-30 0.58(0.43-0.77) 0.54(0.34-0.86)

≥30 0.90(0.57-1.44) 1.58(0.74-3.36)


Parity

0 1 (ref.) 1 (ref.)

1 1.58(0.52-4.79) 2.28(0.62-8.35)

2 2.07(0.73-5.85) 2.45(0.74-8.12)

≥3 5.73(1.98-16.6) 2.89(0.86-9.73)


Menopausal status

Premenopausal 1 (ref.) 1 (ref.)

Postmenopausal 6.93(5.09-9.42) 4.86(2.86-8.25)

Table 16 . Reproductive factors associated with Aromatase inhibitor treated breast cancer patients.

Multivariate OR were mutually adjusted for all reproductive factors.

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Characteristics

　

Non-recur Recur p1

　(N=317) (N=17)

Age at diagnosis (y), mean±SD 59.2 ± 8.72 54.2 ± 11.9 0.1096

< 40 , n(%) 5(2) 2(12)

40-50 26(8) 3(18)

≥50 285(90) 12(71) 0.0058

Age at menarche (y), mean±SD 16.0 ± 1.74 15.9 ± 2.29 0.7895

< 14 , n(%) 74(23) 3(18)

14-15 87(28) 7(41)

> 15 155(49) 7(41) 0.4719

Age at first parturition (y), mean±SD 25.6 ± 4.05 24.4 ± 3.73 0.3321

< 25 , n(%) 157(50) 10(59)

25-30 121(38) 6(35)

≥30 38(12) 1(6) 0.6615

Parity

0 , n(%) 2(1) 2(13)

1 25(9) 2(13)

2 111(40) 4(27)

≥3 141(51) 7(47) 0.0005

Menopausal status

Premenopausal 52(16) 5(29)

Postmenopausal 264(84) 12(71) 0.1671

Tumor size (cm), mean±SD 1.96 ± 1.28 2.19 ± 0.98 0.1841

≤2, n(%) 196(62) 8(47)

> 2 120(38) 9(53)

Node status, n(%)

N0 186(59) 7(41)

N1 85(27) 4(24)

N2+N3 44(14) 6(35) 0.3063

Follow-up (mo), mean±SD 25.5 ± 16.3 26.4 ± 16.5 0.8224

(2) Aromatase inhibitor 치료군의 재발과 관련된 역학적 특성 연구

Table 17.

1 TTEST for continuous variable and χ2 for categorical variable

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Table 18. Cox proportional Hazard models for reproductive factors　

Recur Non-recurHazardRatio1 HazardRatio2

n (%)

Age at diagnosis (y)

< 40 5(2) 2(12) 1 (ref.) 1 (ref.)

40-50 26(8) 3(18) 0.43(0.07-2.61) 0.48(0.06-3.85)

≥50 285(90) 12(71) 0.24(0.05-1.10) 0.06(0.01-0.60)

Age at menarche (y)

< 14 74(23) 3(18) 1 (ref.) 1 (ref.)

14-15 87(28) 7(41) 1.98(0.51-7.68) 10.88(0.91-130)

> 15 155(49) 7(41) 1.33(0.34-5.19) 6.96(0.56-86.3)

Age at first parturition

< 25 157(50) 10(59) 1 (ref.) 1 (ref.)

25-30 121(38) 6(35) 0.76(0.27-2.15) 1.11(0.29-4.21)

≥30 38(12) 1(6) 0.39(0.05-3.10) 0.36(0.03-4.14)

Parity

0 2(1) 2(13) 1 (ref.) 1 (ref.)

1 25(9) 2(13) 0.16(0.02-1.15) 0.01(0.00-0.22)

2 111(40) 4(27) 0.09(0.02-0.51) 0.01(0.00-0.15)

≥3 141(51) 7(47) 0.14(0.03-0.67) 0.03(0.00-0.21)

Menopausal status

Premenopausal 52(16) 5(29) 1 (ref.) 1 (ref.)

Postmenopausal 264(84) 12(71) 0.63(0.22-1.81) 2.66(0.36-19.5)

Tumor size (cm)

≤1 71(22) 2(12) 1 (ref.) 1 (ref.)

> 1 245(78) 15(88) 1.91(0.44-8.38) 7.92(0.61-103)

Hazard Ratio1:Proportional Hazards Regression.

Hazard Ratio2:Proportional Hazards Regression. Mutually adjusted for other reproductive factors.

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　Recur Non-recur

Hazard Ratio1 Hazard Ratio2

n (%)

rs10745940GG 3(11.54) 95(33.81) 1.0(ref) 1.0(ref)

AG 16(61.54) 146(51.96) 2.03(0.79-5.18) 3.64(1.03-12.85)

AA 7(26.92) 40(14.23) 3.02(1.01-9.01) 4.64(1.13-19.01)

rs2978073

CC 9(34.62) 148(52.67) 1.0(ref) 1.0(ref)

CT 15(57.69) 107(38.08) 2.29(1.07-4.91) 3.05(1.27-7.35)

TT 2(7.69) 26(9.25) 1.50(0.33-6.74) 1.70(0.20-14.40)

rs1520220CC 3(11.54) 94(33.45) 1.0(ref) 1.0(ref)

CG 16(61.54) 145(51.60) 2.03(0.80-5.19) 3.63(1.03-12.84)

GG 7(26.92) 42(14.95) 2.96(0.99-8.83) 4.60(1.12-18.85)

rs2981579

CC 7(26.92) 89(31.67) 1.0(ref) 1.0(ref)

CT 6(23.08) 139(49.47) 0.37(0.15-0.92) 0.39(0.14-1.06)

TT 13(50.00) 53(18.86) . .

rs1884054CC 12(46.15) 165(58.72) 1.0(ref) 1.0(ref)

AC 13(50.00) 98(34.88) 1.73(0.83-3.60) 1.30(0.56-3.04)

AA 0(0.00) 18(6.41) 0(0.00) 0(0.00)

rs2981582

CC 10(38.46) 127(45.20) 1.0(ref) 1.0(ref)

CT 6(23.08) 131(46.62) 0.52(0.20-1.37) 0.50(0.17-1.50)

TT 10(38.46) 23(8.19) 2.88(1.24-6.68) 2.23(0.83-5.99)

rs2289046AA 2(7.69) 87(30.96) 1.0(ref) 1.0(ref)

AG 16(61.54) 142(50.53) 1.86(0.73-4.75) 1.96(0.62-6.15)

GG 8(30.77) 52(18.51) 3.49(1.16-10.56) 5.89(1.64-21.14)

rs978458

GG 3(11.54) 93(33.10) 1.0(ref) 1.0(ref)

AG 16(61.54) 147(52.31) 2.00(0.78-5.11) 3.55(1.01-12.54)

AA 7(26.92) 41(14.59) 2.98(1.00-8.89) 4.54(1.11-18.60)Hazard Ratio1:Proportional Hazards Regression.


(3) Aromatase inhibitor 치료군의 재발과 관련된 SNPs 분석

Table 19-1. Association between SNPs and the risk of breast cancer

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Table 19-2. Association between SNPs and the risk of breast cancer 　

Recur Non-recurHazard Ratio1 Hazard Ratio2

n (%)

rs5742667

CC 3(11.54) 91(32.38) 1.0(ref) 1.0(ref)

CT 15(57.69) 149(53.02) 1.85(0.72-4.77) 3.53(1.00-12.48)

TT 8(30.77) 41(14.59) 3.38(1.17-9.78) 4.53(1.1-18.53)

rs754204

CC 20(76.92) 134(47.69) 1.0(ref) 1.0(ref)

CT 5(19.23) 115(40.93) 0.25(0.10-0.67) 0.32(0.11-0.95)

TT 20(76.92) 134(47.69) 0.29(0.04-2.11) 0.37(0.05-2.78)

rs1574213

GG 19(73.08) 177(62.99) 1.0(ref) 1.0(ref)

AG 5(19.23) 92(32.74) 0.66(0.25-1.75) 0.80(0.30-2.18)

AA 1(3.85) 12(4.27) 0.99(0.13-7.34) 0(0.00)

rs183642

AA 9(34.62) 69(24.56) 1.0(ref) 1.0(ref)

AG 13(50.00) 143(50.89) 0.58(0.27-1.27) 0.68(0.27-1.67)

GG 3(11.54) 69(24.56) 0.46(0.13-1.61) 0.72(0.19-2.71)

rs2235515

GG 13(50.00) 78(27.76) 1.0(ref) 1.0(ref)

AG 10(38.46) 151(53.74) 0.40(0.18-0.89) 0.33(0.12-0.91)

AA 2(7.69) 52(18.51) 0.25(0.06-1.07) 0.22(0.05-0.97)

rs3020396

GG 10(38.46) 124(44.13) 1.0(ref) 1.0(ref)

AG 12(46.15) 120(42.70) 0.78(0.37-1.67) 0.74(0.31-1.77)

AA 1(3.85) 37(13.17) 0.37(0.05-2.81) 0.39(0.05-2.97)

rs3731239

TT 21(80.77) 215(76.51) 1.0(ref) 1.0(ref)

CT 3(11.54) 62(22.06) 0.46(0.14-1.52) 0.43(0.12-1.51)

CC 1(3.85) 4(1.42) 0.99(0.13-7.40) 1.75(0.22-13.57)

rs3891248

TT 10(38.46) 85(30.25) 1.0(ref) 1.0(ref)

AT 10(38.46) 149(53.02) 0.53(0.24-1.20) 0.66(0.26-1.69)

AA 5(19.23) 47(16.73) 0.75(0.27-2.09) 0.85(0.27-2.68)

rs4966012

GG 16(61.54) 138(49.11) 1.0(ref) 1.0(ref)

CG 8(30.77) 119(42.35) 0.64(0.28-1.46) 0.62(0.26-1.50)

CC 1(3.85) 24(8.54) 0.44(0.06-3.31) 0(0.00)

Hazard Ratio1:Proportional Hazards Regression.


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Table 19-3. Association between SNPs and the risk of breast cancer 　 Recur Non-recur HazardRatio1 HazardRatio2

n (%)rs10035564GG 14 (53.85) 58 (20.64) 1.0(ref) 1.0(ref)AG 5 (26.92) 135 (48.04) 0.23(0.09-0.58) 0.21(0.07-0.64)AA 7 (19.23) 88 (31.32) 0.26(0.10-0.71) 0.27(0.09-0.81)rs1010167CC 19 (73.08) 142 (50.53) 1.0(ref) 1.0(ref)CG 7 (26.92) 113 (40.21) 0.51(0.22-1.19) 0.45(0.16-1.21)GG 0 ( 0.00) 26 ( 9.25) 0.00(0.00.) 0.00(0.00)rs1048943AA 19 (73.08) 178 (63.35) 1.0(ref) 1.0(ref)AG 6 (23.08) 96 (34.16) 0.56(0.23-1.38) 0.47(0.17-1.31)GG 1 ( 3.85) 7 ( 2.49) 1.04(0.14-7.74) 0.78(0.10-6.07)rs11572126GG 9 (34.62) 133 (47.33) 1.0(ref) 1.0(ref)AG 12 (46.15) 124 (44.13) 1.10(0.49-2.46) 1.14(0.45-2.93)AA 5 (19.23) 24 ( 8.54) 2.53(0.90-7.11) 3.31(1.08-10.16)rs11630479GG 16 (61.54) 138 (49.11) 1.0(ref) 1.0(ref)AG 9 (34.62) 118 (41.99) 0.74(0.33-1.63) 0.61(0.25-1.50)AA 1 ( 3.85) 25 ( 8.90) 0.42(0.06-3.12) 0.00(0.00)rs11632903CC 11 (42.31) 84 (29.89) 1.0(ref) 1.0(ref)CT 13 (50.00) 149 (53.02) 0.52(0.24-1.11) 0.61(0.25-1.45)TT 2 ( 7.69) 48 (17.08) 0.36(0.08-1.55) 0.54(0.12-2.51)rs11732292AA 15 (57.69) 116 (41.28) 1.0(ref) 1.0(ref)AC 9 (34.62) 127 (45.20) 0.61(0.27-1.36) 0.66(0.28-1.53)CC 2 ( 7.69) 37 (13.17) 0.55(0.13-2.40) 0.00(0.00)rs11807AA 21 (80.77) 227 (80.78) 1.0(ref) 1.0(ref)AG 5 (19.23) 50 (17.79) 0.68(0.24-1.97) 0.65(0.19-2.20)GG 0 ( 0.00) 4 ( 1.42) 0.00(0.00) 0.00(0.00)rs1202184AA 14 (53.85) 121 (43.06) 1.0(ref) 1.0(ref)AG 9 (34.62) 113 (40.21) 0.68(0.30-1.53) 0.69(0.28-1.70)GG 3 (11.54) 42 (14.95) 0.68(0.22-2.62) 0.94(0.26-3.39)HazardRatio1: Univariate Hazard Regression Model. HazardRatio2: Multivariate Hazard Regression Model.

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Table 19-4. Association between SNPs and the risk of breast cancer 　 Recur Non-recur HazardRatio1 HazardRatio2n (%)

rs1332018TT 21 (80.77) 197 (70.11) 1.0(ref) 1.0(ref)GT 5 (19.23) 77 (27.40) 0.73(0.28-1.91) 0.74(0.22-2.54)GG 0 ( 0.00) 7 ( 2.49) 0.00(0.00) 0.00(0.00)rs1800896AA 24 (92.31) 232 (82.56) 1.0(ref) 1.0(ref)AG 2 ( 7.69) 49 (17.44) 0.30(0.07-1.27) 0.39(0.09-1.73)GG 0 ( 0.00) 0 ( 0.00) 0.00(0.00) 0.00(0.00)rs1884051GG 11 (42.31) 91 (32.38) 1.0(ref) 1.0(ref)AG 10 (38.46) 132 (46.98) 0.50(0.22-1.14) 0.50(0.188-1.34)AA 5 (19.23) 58 (20.64) 0.78(0.28-2.17) 0.87(0.30-2.52)rs1978095TT 15 (57.69) 160 (56.94) 1.0(ref) 1.0(ref)CT 9 (34.62) 107 (38.08) 0.87(0.39-1.93) 0.67(0.27-1.66)CC 2 ( 7.69) 14 ( 4.98) 0.43(0.06-3.20) 0.77(0.10-5.91)rs2008691GG 3 (11.54) 21 ( 7.47) 1.0(ref) 1.0(ref)AG 7 (26.92) 107 (38.08) 0.40(0.14-1.20) 0.26(0.06-1.08)AA 16 (61.54) 153 (54.45) 0.64(0.25-1.65) 0.62(0.20-1.92)rs2010963GG 14 (53.85) 95 (33.81) 1.0(ref) 1.0(ref)CG 9 (34.62) 132 (46.98) 0.64(0.29-1.45) 0.60(0.24-1.52)CC 3 (11.54) 54 (19.22) 0.36(0.11-1.22) 0.60(0.17-2.15)rs2037498AA 14 (53.85) 181 (64.41) 1.0(ref) 1.0(ref)AG 11 (42.31) 85 (30.25) 1.70(0.79-3.64) 2.47(1.07-5.72)GG 1 ( 3.85) 15 ( 5.34) 0.70(0.09-5.28) 0.00(0.00)rs2070959AA 16 (61.54) 159 (56.58) 1.0(ref) 1.0(ref)AG 9 (34.62) 105 (37.37) 0.69(0.30-1.56) 0.51(0.19-1.38)GG 1 ( 3.85) 17 ( 6.05) 0.57(0.08-4.29) 0.61(0.08-4.69)rs2008691GG 3 (11.54) 21 ( 7.47) 1.0(ref) 1.0(ref)AG 7 (26.92) 107 (38.08) 0.40(0.14-1.20) 0.26(0.06-1.08)AA 16 (61.54) 153 (54.45) 0.64(0.25-1.65) 0.62(0.20-1.92)Hazard Ratio1: Univariate Hazard Regression Model. Hazard Ratio2: Multivariate Hazard Regression Model.

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rs2010963GG 14 (53.85) 95 (33.81) 1.0(ref) 1.0(ref)CG 9 (34.62) 132 (46.98) 0.64(0.29-1.45) 0.60(0.24-1.52)CC 3 (11.54) 54 (19.22) 0.36(0.11-1.22) 0.60(0.17-2.15)rs2037498AA 14 (53.85) 181 (64.41) 1.0(ref) 1.0(ref)AG 11 (42.31) 85 (30.25) 1.70(0.79-3.64) 2.47(1.07-5.72)GG 1 ( 3.85) 15 ( 5.34) 0.70(0.09-5.28) 0.00(0.00)rs2070959AA 16 (61.54) 159 (56.58) 1.0(ref) 1.0(ref)AG 9 (34.62) 105 (37.37) 0.69(0.30-1.56) 0.51(0.19-1.38)GG 1 ( 3.85) 17 ( 6.05) 0.57(0.08-4.29) 0.61(0.08-4.69)rs2168945TT 14 (53.85) 117 (41.64) 1.0(ref) 1.0(ref)GT 10 (38.46) 127 (45.20) 0.71(0.33-1.55) 0.78(0.34-1.80)GG 2 ( 7.69) 37 (13.17) 0.58(0.13-2.54) 0.00(0.00)rs2180341AA 17 (65.38) 147 (52.31) 1.0(ref) 1.0(ref)AG 8 (30.77) 111 (39.50) 0.75(0.33-1.71) 0.41(0.15-1.14)GG 1 ( 3.85) 23 ( 8.19) 0.74(0.10-5.58) 0.77(0.10-5.89)rs2228480GG 20 (76.92) 192 (68.33) 1.0(ref) 1.0(ref)AG 6 (23.08) 79 (28.11) 0.76(0.31-1.86) 0.67(0.24-1.84)AA 0 ( 0.00) 9 ( 3.20) 0.00(0.00) 0.00(0.00)rs2237023TT 6 (23.08) 107 (38.08) 1.0(ref) 1.0(ref)CT 13 (50.00) 136 (48.40) 1.18(0.50-2.76) 2.31(0.77-6.99)CC 7 (26.92) 38 (13.52) 1.92(0.71-5.20) 3.50(1.00-12.23)rs2273535TT 13 (50.00) 121 (43.06) 1.0(ref) 1.0(ref)AT 11 (42.31) 130 (46.26) 0.64(0.29-1.39) 0.77(0.32-1.88)AA 2 ( 7.69) 30 (10.68) 0.49(0.11-2.14) 0.56(0.12-2.69)rs2298016CC 13 (50.00) 123 (43.77) 1.0(ref) 1.0(ref)CG 11 (42.31) 127 (45.20) 0.65(0.30-1.42) 0.78(0.32-1.91)GG 2 ( 7.69) 31 (11.03) 0.47(0.11-2.04) 0.54(0.11-2.59)Hazard Ratio1: Univariate Hazard Regression Model. Hazard Ratio2: Multivariate Hazard Regression Model.

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rs2304000CC 15 (57.69) 110 (39.15) 1.0(ref) 1.0(ref)CG 8 (30.77) 138 (49.11) 0.44(0.19-1.00) 0.49(0.20-1.22)GG 3 (11.54) 33 (11.74) 0.63(0.19-2.14) 0.39(0.09-1.79)rs2411453CC 16 (61.54) 173 (61.57) 1.0(ref) 1.0(ref)AC 8 (30.77) 95 (33.81) 0.68(0.30-1.55) 0.81(0.32-2.03)AA 2 ( 7.69) 13 ( 4.63) 0.47(0.06-3.51) 0.67(0.09-5.13)rs2470144GG 14 (53.85) 112 (39.86) 1.0(ref) 1.0(ref)AG 8 (30.77) 134 (47.69) 0.49(0.21-1.14) 0.76(0.31-1.89)AA 4 (15.38) 35 (12.46) 0.63(0.21-1.89) 0.60(0.17-2.15)rs2520464AA 11 (42.31) 99 (35.23) 1.0(ref) 1.0(ref)AG 11 (42.31) 129 (45.91) 0.77(0.35-1.70) 0.69(0.28-1.73)GG 4 (15.38) 53 (18.86) 0.76(0.25-2.32) 0.90(0.28-2.92)rs2687075CC 14 (53.85) 183 (65.12) 1.0(ref) 1.0(ref)CT 11 (42.31) 84 (29.89) 1.70(0.79-3.64) 2.46(1.06-5.70)TT 1 ( 3.85) 14 ( 4.98) 0.73(0.10-5.49) 0.00(0.00)rs28757078TT 16 (61.54) 135 (48.04) 1.0(ref) 1.0(ref)CT 9 (34.62) 129 (45.91) 0.66(0.30-1.46) 0.66(0.28-1.51)CC 1 ( 3.85) 17 ( 6.05) 0.71(0.09-5.41) 0.67(0.09-5.19)rs2946834CC 3 (11.54) 86 (30.60) 1.0(ref) 1.0(ref)CT 15 (57.69) 148 (52.67) 1.55(0.60-4.01) 3.09(0.86-11.08)TT 8 (30.77) 46 (16.37) 2.74(0.95-7.94) 4.65(1.18-18.35)rs3176336TT 15 (57.69) 138 (49.11) 1.0(ref) 1.0(ref)AT 10 (38.46) 117 (41.64) 0.52(0.24-1.17) 0.51(0.20-1.27)AA 1 ( 3.85) 26 ( 9.25) 0.26(0.03-1.93) 0.27(0.04-2.11)rs3754446GG 16 (61.54) 152 (54.09) 1.0(ref) 1.0(ref)GT 9 (34.62) 107 (38.08) 0.73(0.32-1.67) 0.71(0.26-1.98)TT 1 ( 3.85) 22 ( 7.83) 0.32(0.04-2.36) 0.39(0.05-2.96)Hazard Ratio1: Univariate Hazard Regression Model. Hazard Ratio2: Multivariate Hazard Regression Model.

- 96 -


rs3757823TT 7 (26.92) 73 (25.98) 1.0(ref) 1.0(ref)CT 11 (42.31) 133 (47.33) 0.77(0.33-1.82) 0.53(0.19-1.50)CC 8 (30.77) 75 (26.69) 1.00(0.40-2.50) 0.75(0.26-2.13)rs3768704GG 10 (38.46) 92 (32.74) 1.0(ref) 1.0(ref)AG 14 (53.85) 140 (49.82) 0.70(0.33-1.50) 0.89(0.37-2.15)AA 2 ( 7.69) 49 (17.44) 0.30(0.07-1.31) 0.42(0.09-1.94)rs3798577TT 13 (50.00) 112 (39.86) 1.0(ref) 1.0(ref)CT 11 (42.31) 138 (49.11) 0.73(0.34-1.58) 0.82(0.35-1.94)CC 2 ( 7.69) 31 (11.03) 0.78(0.18-3.41) 0.60(0.08-4.75)rs3809865AA 19 (73.08) 167 (59.43) 1.0(ref) 1.0(ref)AT 7 (26.92) 101 (35.94) 0.68(0.29-1.61) 0.59(0.22-1.60)TT 0 ( 0.00) 13 ( 4.63) 0.00( 0.00) 0.00(0.00)rs38858TT 10 (38.46) 100 (35.59) 1.0(ref) 1.0(ref)GT 14 (53.85) 130 (46.26) 0.95(0.45-2.04) 0.89(0.36-2.18)GG 2 ( 7.69) 50 (17.79) 0.52(0.12-2.32) 0.78(0.17-3.64)rs3889391GG 15 (57.69) 119 (42.35) 1.0(ref) 1.0(ref)AG 9 (34.62) 127 (45.20) 0.53(0.24-1.17) 0.61(0.25-1.49)AA 2 ( 7.69) 35 (12.46) 0.48(0.11-2.07) 0.64(0.14-2.97)rs41736TT 9 (34.62) 69 (24.56) 1.0(ref) 1.0(ref)CT 14 (53.85) 143 (50.89) 0.68(0.31-1.47) 0.82(0.33-2.06)CC 3 (11.54) 69 (24.56) 0.49(0.14-1.75) 0.80(0.20-3.05)rs41739GG 9 (34.62) 69 (24.56) 1.0(ref) 1.0(ref)AG 14 (53.85) 144 (51.25) 0.67(0.31-1.47) 0.82(0.33-2.04)AA 3 (11.54) 68 (24.20) 0.50(0.14-1.78) 0.81(0.21-3.11)rs4246340AA 10 (38.46) 76 (27.05) 1.0(ref) 1.0(ref)AC 11 (42.31) 148 (52.67) 0.49(0.22-1.11) 0.59(0.24-1.46)CC 5 (19.23) 57 (20.28) 0.82(0.29-2.31) 0.48(0.13-1.73)Hazard Ratio1: Univariate Hazard Regression Model. Hazard Ratio2: Multivariate Hazard Regression Model.

- 97 -


rs4494250GG 16 (61.54) 185 (65.84) 1.0(ref) 1.0(ref)AG 9 (34.62) 86 (30.60) 0.93(0.42-2.06) 0.80(0.30-2.08)AA 1 ( 3.85) 10 ( 3.56) 0.80(0.11-5.97) 0.53(0.07-4.13)rs4646447GG 14 (53.85) 191 (67.97) 1.0(ref) 1.0(ref)AG 11 (42.31) 80 (28.47) 1.95(0.91-4.17) 2.90(1.29-6.97)AA 1 ( 3.85) 10 ( 3.56) 0.86(0.11-6.46) 0.00(0.00)rs4647907GG 15 (57.69) 110 (39.15) 1.0(ref) 1.0(ref)AG 8 (30.77) 138 (49.11) 0.44(0.19-1.00) 0.49(0.20-1.22)AA 3 (11.54) 33 (11.74) 0.63(0.18-2.14) 0.39(0.09-1.79)rs4773082TT 21 (80.77) 155 (55.16) 1.0(ref) 1.0(ref)CT 4 (15.38) 98 (34.88) 0.29(0.10-0.84) 0.32(0.09-1.11)CC 1 ( 3.85) 28 ( 9.96) 0.39(0.05-2.93) 0.58(0.08-4.40)rs4775934TT 19 (73.08) 187 (66.55) 1.0(ref) 1.0(ref)CT 7 (26.92) 88 (31.32) 0.62(0.25-1.53) 0.68(0.25-1.85)CC 0 ( 0.00) 6 ( 2.14) 0.00(0.00) 0.00(0.00)rs4807542GG 20 (76.92) 192 (68.33) 1.0(ref) 1.0(ref)AG 5 (19.23) 77 (27.40) 0.77(0.29-2.03) 0.62(0.18-2.15)AA 1 ( 3.85) 12 ( 4.27) 0.72(0.10-5.33) 0.68(0.08-5.44)rs4970773GG 16 (61.54) 149 (53.02) 1.0(ref) 1.0(ref)CG 9 (34.62) 108 (38.43) 0.76(0.33-1.73) 0.76(0.27-2.10)CC 1 ( 3.85) 24 ( 8.54) 0.30(0.04-2.24) 0.36(0.05-2.743rs511298CC 16 (61.54) 187 (66.55) 1.0(ref) 1.0(ref)CT 8 (30.77) 83 (29.54) 1.16(0.50-2.66) 1.33(0.52-3.35)TT 2 ( 7.69) 11 ( 3.91) 4.23(0.96-18.66) 6.01(1.30-27.84)rs570613AA 11 (42.31) 112 (39.86) 1.0(ref) 1.0(ref)AG 14 (53.85) 134 (47.69) 0.95(0.40-1.99) 0.83(0.35-1.95)GG 1 ( 3.85) 35 (12.46) 0.27(0.04-2.01) 0.45(0.06-3.54)Hazard Ratio1: Univariate Hazard Regression Model. Hazard Ratio2: Multivariate Hazard Regression Model.

- 98 -


rs6810872GG 6 (23.08) 107 (38.08) 1.0(ref) 1.0(ref)CG 13 (50.00) 136 (48.40) 1.18(0.50-2.76) 2.31(0.77-6.99)CC 7 (26.92) 38 (13.52) 1.92(0.71-5.20) 3.50(1.00-12.23)rs699947CC 12 (46.15) 152 (54.09) 1.0(ref) 1.0(ref)AC 12 (46.15) 102 (36.30) 1.33(0.61-2.87) 0.84(0.34-2.09)AA 2 ( 7.69) 27 ( 9.61) 0.57(0.13-2.50) 0.56(0.12-2.49)rs712221AA 12 (46.15) 83 (29.54) 1.0(ref) 1.0(ref)AT 13 (50.00) 143 (50.89) 0.70(0.33-1.47) 0.64(0.28-1.48)TT 1 ( 3.85) 55 (19.57) 0.17(0.02-1.28) 0.00(0.00rs750686AA 11 (42.31) 95 (33.81) 1.0(ref) 1.0(ref)AG 8 (30.77) 137 (48.75) 0.43(0.18-1.04) 0.54(0.20-1.44)GG 7 (26.92) 49 (17.44) 0.92(0.37-2.30) 0.99(0.35-2.78)rs752760TT 14 (53.85) 109 (38.79) 1.0(ref) 1.0(ref)CT 7 (26.92) 134 (47.69) 0.43(0.18-1.03) 0.66(0.26-1.69)CC 5 (19.23) 38 (13.52) 0.73(0.27-1.99) 0.73(0.23-2.29)rs7696175CC 20 (76.92) 210 (74.73) 1.0(ref) 1.0(ref)CT 5 (19.23) 63 (22.42) 0.62(0.21-1.78) 0.72(0.24-2.14)TT 1 ( 3.85) 8 ( 2.85) 0.78(0.10-5.74) 0.63(0.08-5.06)rs7703618GG 16 (61.54) 131 (46.62) 1.0(ref) 1.0(ref)AG 8 (30.77) 119 (42.35) 0.49(0.21-1.17) 0.62(0.24-1.59)AA 2 ( 7.69) 31 (11.03) 0.54(0.13-2.33) 0.37(0.05-2.77)rs776746GG 14 (53.85) 184 (65.48) 1.0(ref) 1.0(ref)AG 11 (42.31) 83 (29.54) 1.82(0.85-3.91) 2.84(1.21-6.68)AA 1 ( 3.85) 14 ( 4.98) 0.74(0.10-5.59) 0.00(0.00)rs7776136TT 17 (65.38) 147 (52.31) 1.0(ref) 1.0(ref)AT 8 (30.77) 109 (38.79) 0.76(0.33-1.73) 0.42(0.15-1.15)AA 1 ( 3.85) 24 ( 8.54) 0.69(0.09-5.22) 0.72(0.09-5.57)Hazard Ratio1: Univariate Hazard Regression Model. Hazard Ratio2: Multivariate Hazard Regression Model.

- 99 -


rs7987237CC 14 (53.85) 157 (55.87) 1.0(ref) 1.0(ref)CT 11 (42.31) 111 (39.50) 0.83(0.39-1.77) 0.67(0.27-1.63)TT 1 ( 3.85) 13 ( 4.63) 0.70(0.09-5.26) 0.44(0.06-3.45)rs8042086CC 11 (42.31) 84 (29.89) 1.0(ref) 1.0(ref)CT 13 (50.00) 149 (53.02) 0.53(0.24-1.11) 0.61(0.25-1.45)TT 2 ( 7.69) 48 (17.08) 0.36(0.08-1.55) 0.54(0.12-2.51)rs851984CC 22 (84.62) 206 (73.31) 1.0(ref) 1.0(ref)CT 4 (15.38) 72 (25.62) 0.57(0.20-1.65) 0.52(0.15-1.79)TT 0 ( 0.00) 3 ( 1.07) 0.00(0.00) 0.00(0.00)rs9559654GG 21 (80.77) 184 (65.48) 1.0(ref) 1.0(ref)AG 5 (19.23) 83 (29.54) 0.66(0.25-1.73) 0.48(0.14-1.63)AA 0 ( 0.00) 14 ( 4.98) 0.00(0.00) 0.00(0.00)rs978458GG 3 (11.54) 93 (33.10) 1.0(ref) 1.0(ref)AG 16 (61.54) 147 (52.31) 2.00(0.78-5.10) 3.55(1.01-12.54)AA 7 (26.92) 41 (14.59) 2.98(1.00-8.90) 4.54(1.11-18.60)HazardRatio1: Univariate Hazard Regression Model. HazardRatio2: Multivariate Hazard Regression Model.

- 100 -

Figure 7-1. Interaction between SNPs and Survival graph.

- 101 -


- 102 -


- 103 -


- 104 -


- 105 -

○ 과제시작시점부터 과제종료시점까지의 연구성과(학술지 게재, 학회발표, 학위논문, 산업재산권 출원․등록, 워크샾 또는 심포지움 개최, 전시회 참가, 임상응용, 기술성과 이전, 벤처 창업 등의 실적)를 기재하되, 본 과제와 관련성이 있는 성과에 한하여 기재

※ 논문, 특허성과는 과제 시작시점이후 게재 신청 또는 출원된 실적만 기재. 다만, 후속과제의 경우는 예외

4. 연구성과 및 목표달성도(1) 연구성과

Study 1: Association of polymorphisms and haplotypes in the insulin-like growth factor 1 receptor (IGF1R) gene with breast cancer in Korean women

Abstract: The insulin-like growth factor (IGF) signaling axis plays an important role

in cancer biology. The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine

kinase growth factor receptor that plays important roles in numerous cellular

functions and signal transduction pathways. IGF1R may also play a role in the

initiation and progression of breast cancer. However, studies of common variation in

the IGF1R gene, involved in steroid hormone and IGF-1 metabolism, have yet to

provide convincing evidence that such variants predict breast cancer risk. We

genotyped 384 tagging single nucleotide polymorphisms (SNPs) in 1026 cases of

breast cancer and 392 age-matched control in a population of Korean women. Of the

384 SNPs, fifty one SNPs in the IGF1R gene were examined for association with

breast cancer in the study. All the SNPs investigated were in Hardy-Weinberg

equilibrium. These SNPs tested were significantly associated with breast cancer risk,

after correction for multiple comparisons stratified by adjusting for age at diagnosis,

BMI, age at menarche, and age at first parturition. Among 51 IGF1R SNPs, three

intron located SNPs (rs8032477, rs11635251, and rs12916884) with homozygous

genotype (variant genotype) had increased risk of breast cancer (OR(CI 95%):

0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)). Seven of the 51 IGF1R SNPs were

in LD and in one haplotype block, and were likely to be associated with breast

cancer risk. Overall, this comprehensive case-control study found statistically

significant associations between breast cancer risk and polymorphisms in IGF1R gene.

Taking the status of the IGF1R polymorphism into consideration, our results may

help in improving the ability to develop effective treatment modalities for those

- 106 -

conditions in which IGF1R is involved. To the best of our knowledge, this study is

the first to demonstrate the association between IGF1R polymorphisms with the risk

of breast cancer.

Study 2: Genetic variation in candidate obesity genes IGF1, IRS2, and IGF1R and the risk of triple-negative breast cancer in Korean women

Abstract: Obesity has consistently been associated with breast cancer risk, as bodymass may play a role in breast tumor development, and thus the role ofinsulin-related pathway have been hypothesized. However, the interaction of obesityrelated genes and BMI in triple-negative breast cancer has not been previouslystudied.

Single nucleotide polymorphisms (SNPs) were genotyped across IGF1, IRS2, and

IGF1R genes in 392-age matched controls and 1026 cases including 328

triple-negative tumor subtype case. Logistic regression models were used to examine

the association between each SNP and risk for triple-negative breast cancer while

adjusting for matching factors and potential confounders. We also examined whether

these SNPs were associated with measures of obesity (BMI).

Eight SNPs each in IGF1 and IRS2, and twenty nine SNPs in IGF1R were associated

with triple-negative breast cancer (p trend = <0.05). Among these, four SNPs in

IRS2 and twenty three SNPs in IGF1R were associated with increased risk of

triple-negative breast cancer and high BMI (P for interaction = <0.05). The IGF1R

rs4966009 and rs4966007, IRS2 rs7987237, and IGF1 rs35765, with minor allele

frequencies 16.2 and 16.7, 5.6, and 0.3%, showed highest association with the risk of

triple-negative breast cancer in obese women (OR(95%CI), 3.34(1.91-5.86) and

3.29(1.89-5.74), 2.81(1.56-5.07), 2.68(1.63-8.77); P = <0.0068). IRS2 marker rs2289046

was also associated with the risk in obese TNBC subjects.

Our findings suggest that SNPs in IRS2, IGF1R, and IGF1 marked regions of the

genome may harbor risk alleles for triple-negative breast cancer, and these

associations may be influenced by adiposity or high BMI. Further the association

between insulin-related genes and breast cancer risk among Korean women may be

dependent on estrogen exposure as observed exclusively in TNBC subjects.

- 107 -

논문명 저자(저자구분1)) 저널명(I.F.) Year;Vol(No):Page 구분2) 지원과제번호3)

Methylation patterns of genes codingfor drug-metabolizing enzymes intamoxifen-resistant breast cancertissues.

강한성(교신)

Journal of

Molecular

Medicine

(5.064)

2010

;88(11):1123-31.국외SCI

0910310-3

Hypomethylation of theinterleukin-10 gene in breast cancertissues.

강한성(교신)

Breast

(2.172)2010 Jun 18. 국외

SCI

0910310-3

Differential methylation hybridizationprofiling identifies involvement ofSTAT1-mediated pathways in breastcancer.

강한성(교신) Int J Oncol.

2011 Oct;39(4):955-63.

국외SCI

0910310-3

Accumulation of p53 determined byimmunohistochemistry as a prognosticmarker in node negative breastcancer; analysis according to StGallen consensus and intrinsicsubtypes.

강한성(교신)

J SurgOncol.

2011 Mar1;103(3):207-11.

국외SCI

0910310-3

Predictor of recurrence in the triplenegative breast cancer (tentative)

Breast Cancer Research and Treatment (4.85)국외SCI

0910310-3

Genome-wide association study in EastAsians identifies novel susceptibilityloci for breast cancer

김미경(공동), 강한성(공동)PLoS Genetics(9.543) In press 국외SCI

0910310-3

Genetic variation in candidate obesitygenes IGF1, IRS2, and IGF1R and therisk of triple-negative breast cancer inKorean women

강한성(제1) 김미경(교신)Breast Cancer Research (5.79)


0910310-3

Association of polymorphisms andhaplotypes in the insulin-like growthfactor 1 receptor (IGF1R) gene withbreast cancer in Korean women

강한성(제1) 김미경(교신)Breast Cancer Research and Treatment (4.85)


0910310-3

논문명 저자 학술대회명 지역1) 지원과제번호Association of polymorphisms and haplotypes in the insulin-like

김미경, 강한성,

미국암학회(AACR) 미국, 시카고 0910310-3

가. 국내 및 국제 전문학술지 논문 게재 및 신청

1) 저자구분 : 교신, 제1, 공동2) 구분 : 국내, 국내 SCI, 국내 SCIE, 국외, 국외SCI, 국외SCIE 등3) 지원과제번호(Acknowledgement) - 과제번호를 연차 표시(-1, -2, -3 등)를 생략하고 7자리로 기재하고, 과제와 관련성은 있으나

불가피하게 Acknowledgement가 누락된 경우에는 ‘없음’으로 기재

나. 국내 및 국제 학술대회 논문 발표

- 108 -

growth factor 1 receptor (IGF1R) gene with breast cancer in Korean women.

홍경만

구분1) 특허명 출원인 출원국 출원번호

저서명 저자 발행기관(발행국, 도시) 쪽수 Chapter 제목, 쪽수(공저일 경우)

보고서명 정부정책 기여내용

1) 지역 : 국내, 국외다. 산업재산권

1) 구분 : 발명특허, 실용신안, 의장등록 등라. 저 서

마. 연구성과의 정부정책 기여

바. 기타연구성과

- 109 -

최종목표 연차별목표 달성내용 달성도(%)연차 최종

1 . 삼 중 음 성 와 HER2 (+) 환자군에서 재발군과 재발하지 않는 군 사이에 암조직에서 발현이 달라지는 유전자에 대한 정보를 기반으로 두가지 유방암 환자군에서의 치료 반응 표지자를 개발

2. 삼중음성 환자와 HER2 (+) 환자군, ER (+) 유방암환자군의 유방암발생과 관련이 있는 유전적 변이를 찾고 표지자로 개발

1차년도

삼중음성 유방암 환자중 재발환자와 그렇지 않은 환자 각각 50명을 선발하고 암조직에서 두 군 사이에 발현이 달라져 있는 유전자 분석

삼중음성 유방암 환자중 재발환자와 그렇지 않은 환자 각각 50명을 선발하고 암조직에서 두 군 사이에 발현이 달라져 있는 유전자 분석 1 100

삼중음성 유방암환자와 정상대조군 328여명을 대상으로 암발생과 관련된 384 개 SNP를 분석

삼중음성 유방암환자와 정상대조군 328여명을 대상으로 암발생과 관련된 384 개 SNP를 분석

2차년도

HER2양성과 ER, PR양성 유방암에서 재발군과 비재발군 사이의 유전자 발현비교

HER2양성과 ER, PR양성 유방암에서 재발군과 비재발군 사이의 유전자 발현비교

2 100삼중음성 유방암환자에서 재발군과 비재발군 사이 유의한 차이가 나는 유전자의 특성연구

삼중음성 유방암환자에서 재발군과 비재발군 사이 유의한 차이가 나는 유전자의 특성연구



3차년도

SPOCK2 유전자의 특성연구 SPOCK2 유전자의 특성연구

3 1005개 추가 유전자의 유방암 표지자 가능성 검토

5개 추가 유전자의 유방암 표지자 가능성 검토

HER2양성 유방암의 SNP 양상 분석 및 재발군과 비재발군에서 SNP 양상 분석

HER2양성 유방암의 SNP 양상 분석 및 재발군과 비재발군에서 SNP 양상 분석

(2) 목표달성도가. 연구목표의 달성도

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평가의 착안점 자 체 평 가유방암 환자의 발생 및 항암제 치료 반응과 관련된 유전적 특성 규명과 역학적 특성 연구

유방암 환자 1026 명과 대조군 392 명의 임상정보, 역학정보 등을 분석하고 혈액 DNA로부터 SNP 분석 (총 시료 수 (1418 명)

Luminal A 유방암환자 발생 및 치료 반응과 관련된 유전적 특성 규명과 역학적 특성 연구

Luminal A 유방암 환자 345 명의 임상정보, 역학정보 등을 분석하고 혈액 DNA로부터 SNP 분석

Luminal B 유방암환자 발생 및 치료 반응과 관련된 유전적 특성 규명과 역학적 특성 연구

Luminal B 유방암 환자 228 명의 임상정보, 역학정보 등을 분석하고 혈액 DNA로부터 SNP 분석

HER2 양성 유방암환자의 발생 및 치료 반응과 관련된 유전적 특성 규명과 역학적 특성 연구

HER2 양성 유방암 환자 124 명의 임상정보, 역학정보 등을 분석하고 혈액 DNA로부터 SNP 분석

삼중음성 (triple negative) 유방암환자의 발생 및 예후에 미치는 요인에 대한 역학연구 및 SNP 연구

삼중음성 (triple negative) 유방암 환자 328 명의 임상정보, 역학정보 등을 분석하고 혈액 DNA로부터 SNP 분석


AI 치료환자 418 명에 대한 임상정보, 역학정보 등을 분석하고 혈액 DNA로부터 SNP 분석

나. 평가의 착안점에 따른 목표달성도에 대한 자체평가

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5. 연구결과의 활용계획(1) 연구종료 2년후 예상 연구성과

구 분 건 수 비 고학술지 논문 게재 Breast Cancer Research (5.79) Breast Cancer Research and Treatment (4.85)산업재산권 등록 특허 등록 예상 국가,

예상 특허명 등기 타

(2) 연구성과의 활용계획1) 삼중음성 유방암의 전이과정에 대한 분자생물학적 정보제공2) 삼중음성 유방암의 새로운 진단표지자 제공3) 유방암의 세 군을 치료반응에 따라 유전적으로 분류하고 이들의 특성을 연구하며 이를 바탕으

로 한국인 유방암 환자 모델에서 진료 및 치료 지침을 개발할 수 있음4) 유방암의 각 군마다 특징적인 예후인자 규명을 통해 3차 예방을 위한 전략 수립이 가능5) 유방암 환자의 각 군마다 특징적인 유전자-환경 상호관계 연구의 기초자료 제공

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○ 본 연구의 성과로 논문, 저서, 산업재산권, 정책정책 기여 등이 있을 경우 관련 증빙자료를 첨

부토록 함

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49. Joseph J, Niggemann B, Zaenker KS, Entschladen F. The neurotransmitter gamma-aminobutyric acid is an inhibitory regulator for the migration of SW 480 colon carcinoma cells. Cancer Res. 2002 Nov 15;62(22):6467-9.

7. 첨부서류

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전화번호031-920-1220전 자 우 편[email protected] 색인단어 국문 유방암환자, 삼중음성, 분자표지자, 에스트로겐 수용체, 프로게스테론 수용 체,