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The relationship between vitamin B6 and colonrectal cancer risk維生素 B6 與大腸癌罹患風險之關係

實習生：王培竹指導營養師：林京美 營養師報告日期： 2012/12/25

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Vitamin B6

• Vitamin B6 is a water-soluble vitamin present in the human body as pyridoxine, pyridoxal, and pyridoxamine

• RDI：– 1.4 mg/d (♂) – 1.2 mg/d (♀)

• The main dietary sources ：– poultry, fish, and meat– whole grains, legumes, and nuts

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Vitamin B6

• Regulation：– oxidative stress– immune system– carcinogenesis

• Low levels of vitamin B6：– cell proliferation ↑– C-reactive protein ↑– oxidative stress ↑– nitric oxide synthesis ↑– angiogenesis ↑

aberrations in DNA methylationimbalance in DNA precursorsdisruption in DNA repair

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Vitamin B6One-carbon metabolism

Vitamin B6

Vitamin B6

Vitamin B6

Folic acid

OxidationDetoxification

DNA synthesis

DNA methylationMTHFR

Vitamin B12

J.E. de Wit, 2011

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CRC risk

PlasmaVit.B

Dietary Vit.B6

PlasmaVit.B6

CRC ： colorectal cancer

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Dietary vitamin B6 intake and the risk of colorectal

cancerTheodoratou E, et al. Cancer Epidemiol Biomarkers Prev. 2008;17(1):171–82.

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Background

• evaluate the effect of dietary and supplementary intake of vitamin B6 on CRC and to investigate whether vitamin B6 effects are modified by folate and alcohol intakes.

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Exclusions death before ascertainmenttoo ill to participaterecurrent casesunable to give informed consent( learning difficulties or other Medical conditions.)

macronutrients, micronutrients

CRCn=2028, 16-79 yr

No-CRCn=2722, 16-79 yr

Information question (lifestyle, cancer)Semiquantitative FFQ (150 foods)

≦55 yr

MTHFR, MTR, MTRR genotypes

DNA samples were accuratelyquantified by PicoGreen

CRCn=1001

No-CRCn=1010

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Approximately 20%-30% reduction in risk for those of high versus those of low intake

Intakes of dietary and of total Vit.B6 showed a significant inverse, and dose-dependent effect on CRC risk in all models.

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Vit.B6 (dietary and total) had a similar strong inverse association with both colon, rectal, proximal, and distal cancer.

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Vit.B6 effect was stronger among females.

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Vit.B6 effect was stronger among ≦55 years.

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Vit.B6 inverse association was of similar strength when adjusting for folate.

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None of the polymorphisms was significantly associated with CRC

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Discussion

• Intakes of dietary vitamin B6 showed a significant, inverse, and dose-dependent effect on CRC risk.

• Intakes of Vitamin B6 supplement did not effect (associated) on CRC risk. The high dietary vitamin B6 intake from food and/or supplements had a lower CRC risk.

• Gene polymorphisms was not significantly associated with CRC.

• Folate and alcohol did not affect the relationship between vitamin B6 and CRC risk.

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Prospective study of plasma vitamin B6 and

risk of colorectal cancer in men

Lee JE, et al. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1197–

202.

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Background

• evaluate the effect of plasma PLP on CRC and whether the association for plasma PLP was independent of plasma levels of one-carbon metabolites and markers of inflammation, including CRP, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6.

2020

Exclusions •myocardial infarction•stroke•transient ischemic attack•cancer (except nonmelanoma skin cancer)•renal or liver disease•peptic ulcer•gout•used vitamin A supplements•used β -carotene supplements

1982

2000 No-CRC, n=371

Physicians’ Health Study n=22071

PLP , Vit.B12, folateHomocysteine , cysteineTNF- α R2 , CRP , IL-6MTHFR C677T

CRC, n=197

Randomized, double-blind, placebo-controlled tial (aspirin and β-carotene )

Self-administered questionnaires12 or 18 m FFQBlood sample, n=14196 (1982-84)

Blood sample

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顯著正相

關

顯著負相

關

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A lower rick of colorectal cancer was observed mainly among participants in the two higher quartiles.

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Discussion

• The significant inverse association between plasma PLP levels and CRC risk.

• MTHFR C677T, inflammatory markers, folate, alcohol, multivitamin, aspirin, beta carotene, and BMI did not affect the relationship between PLP and CRC risk.

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Plasma levels of B vitamins

and colorectal cancer risk:the multiethnic cohort

studyLe Marchand L, et al. Cancer Epidemiol Biomarkers Prev. 2009;18(8):2195–201

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Background

• comprehensively investigate the relationships of plasma folate, pyridoxal-5′-phosphate (PLP, the active form of vitamin B6), vitamin B12, methylmalonic acid, homocysteine, and cysteine with colorectal cancer risk, accounting for suspected modifiers (alcohol intake, MTHFR C677T genotype, and plasma CRP) and potential confounders.

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Blood sample

PLP, Vit.B12, folateMMA, homocysteine, cysteineCRPMTHFR C677T

The multethnic cohort study n=≧215,000

26-page baseline questionnaireFFQBlood sample, n=67594 (2001-06)

No-CRC, n=411CRC, n=224

2006

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12% ＞ 10%

60% ＞ 54%

23% ＞ 11%57% ＞ 52%

＞

＞＞

＜

＜

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Discussion

• The significant inverse association between plasma PLP levels and CRC risk.

• The higher plasma folate can reduce CRC risk.

• Vitamin B12, MMA, cysteine, homocysteine was not significantly associated with CRC risk.

• MTHFR C677T, CRP, alcohol did not significant affect the relationship between PLP and CRC risk.

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CRC risk

PlasmaVit.B

Dietary Vit.B6

PlasmaVit.B6

( - ) association

with LPL and folate ( - ) association

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( - ) association

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Summary

• Finding that higher vitamin B6 intake and plasma PLP levels are associated with a lower risk of colorectal cancer, which is associated with a lower risk of colorectal cancer independent of other one-carbon metabolites, inflammatory biomarkers, MTHFR C677T and alcohol.

the significant inverse association between vitamin B6 levels and CRC risk

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