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Effect of -Carotene Supplementation on the Risk of Lung Cancer. ATBC (Finnland, 1994 >29 000 smokers) β -carotene (20 mg/day/5-8 years) Lung cancer 18% CARET (USA, 1996, 18 000 participants) 30 mg ß -carotene and 25,000 IU retinil- palmitate Lung cancer 28%. - PowerPoint PPT Presentation
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Retrospective studies: Dietary carotenoids and lung cancer risk
Ziegler et al 1984, 1986 Carotenoids Decreased (significant)
Samet et al, 1985 Carotenoids Decreased (significant)
Byers et al, 1987 Carotenoids Decreased (significant)
Pastorino et al, 1987 Carotenoids Decreased (significant)
Marchand et al, 1989 β-carotin Decreased (significant)
Prospective studies: Serum or plasma carotenoids and lung cancer risk
Stahelin et al, 1984, 1990 β-carotene Lower (significant)
Nomura et al, 1985 β-carotene Lower (significant)
Menkes et al, 1986 β-carotene Lower (significant)
Wald et al, 1988 β-carotene Lower (significant)
Connett et al, 1989 β-carotene Lower (significant)
Effect of -Carotene Supplementation on the Risk of Lung Cancer
• ATBC (Finnland, 1994 >29 000 smokers)
β-carotene (20 mg/day/5-8 years)
Lung cancer 18%
• CARET (USA, 1996, 18 000 participants)
30 mg ß-carotene and 25,000 IU retinil- palmitate
Lung cancer 28%
Tea Consumption and Esophageal Cancer I.
• Green tea consumption statistically significantly decreased the risk of esophageal cancer
(OR: 0.50; 95% CI = 0.30-0.830)
(Gao YT, McLaughlin JK, Blot WJ, et al.Reduced risk of esophageal cancer associatedwith green tea consumption.
J Natl Cancer Inst 1994;86:855-888.)
Tea Consumption and Esophageal Cancer II.
Daily tea consumption (g tea leaves) in Northern Iranian regions:
High-risk region Low-risk region
Winter 5.2 3.0
Spring-summer 7.8 5.1
Summer-autumn 4.7 3.9
(Hormozdiari, 1975)
Regular Intake and Supplementation Level of -Carotene
mg/day
Calcium: Dietary Intake and Supplements
mg/day
Factors Affecting the Antioxidant/Prooxidant Properties of
-carotene
• Concentration
• Presence of certain prooxidant compounds
• Oxigene-concentration
• Presence of other antioxidants
Temperature of Tea at Consumption in Different Regions of Iran
Percent of people drinking tea at less
than 55 °C
Percent of people drinking tea at more than 65 °
High-risk region (esophageal cancer)
3% 62%
Low-risk region (esophageal cancer)
72% 19%
(Ghadirian, 1987)
Factors Concerning Tea Consumption
• Sort and quality of tea (green, oolong, black)
• Preparation method (water temperature, soaking time)
• Water quality (hardness, contaminants)
• Quality of dishes, contaminants
• Sweetening (sugar)
• Temperature at consumption
Lifetime Probability of Developing Cancer, by Site, Men, US, 1997-1999
Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
All sites 1 in 2
Prostate 1 in 6
Lung & bronchus 1 in 13
Colon & rectum 1 in 17
Urinary bladder 1 in 29
Non-Hodgkin lymphoma 1 in 47
Melanoma 1 in 57
Leukemia 1 in 69
Oral cavity 1 in 71
Kidney 1 in 72
Stomach 1 in 79
Lifetime Probability of Developing Cancer, by Site, Women, US, 1997-1999
Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
Risk
All sites 1 in 3
Breast 1 in 8
Lung & bronchus 1 in 17
Colon & rectum 1 in 18
Uterine corpus 1 in 37
Non-Hodgkin lymphoma 1 in 56
Ovary 1 in 58
Pancreas 1 in 80
Melanoma 1 in 81
Urinary bladder 1 in 88
Uterine cervix 1 in 123
Cancer Survival*(%) by Site and Race,1992-1998
*5-year relative survival rates based on follow up of patients through 1999. Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
All Sites 64 53 11
Breast (female) 88 73 15
Colon & rectum 63 53 10
Esophagus 15 8 7
Leukemia 47 38 9
Non-Hodgkin lymphoma 56 46 10
Oral cavity 59 35 24
Prostate 98 93 5
Urinary bladder 82 65 17
Uterine cervix 72 60 12
Uterine corpus 86 61 25
White % Difference
AfricanAmerica
n
Relative Survival* (%) during Three Time Periods by Cancer Site
*5-year relative survival rates based on follow up of patients through 1999. Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
1974-1976
1983-1985
1992-1998
• All sites 50 52 62
• Breast (female) 75 78 86
• Colon & rectum 50 57 62
• Leukemia 34 41 46
• Lung & bronchus 12 14 15
• Melanoma 80 85 89
• Non-Hodgkin lymphoma 47 54 55
• Ovary 37 41 53
• Pancreas 3 3 4
• Prostate 67 75 97
• Urinary bladder 73 78 82
Cancer Death Rates*, by Race and Ethnicity, 1992-1999
*Per 100,000, age-adjusted to the 2000 US standard population.†Hispanic is not mutually exclusive from whites, African Americans, Asian/Pacific Islanders, and American Indians.Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
258,1
160,6 154,5 163,7171,2204,5
104,4 110,4 105,7
369,0
0
50
100
150
200
250
300
350
400
White AfricanAmerican
Asian/PacificIslander
AmericanIndian/ Alaskan
Native
Hispanic†
Male
Female
Change in the US Death Rates* by Cause, 1950 & 2000
* Age-adjusted to the 2000 US standard population.Source: US Mortality Volume 1950, National Vital Statistics Report, 2002, Vol. 50, No. 15.
586,8
180,5
48,160,923,7
200,9193,7
258,2
0
100
200
300
400
500
600
HeartDiseases
CerebrovascularDiseases
Pneumonia/Influenza
Cancer
1950
2000
Rate Per 100,000
Cardiovascular Cancer
(% of total mortality)
1993 2003 1993 2003
Male Female Male Female Male Female Male Female
46,28 57,52 45,47 56,54 22,63 20,53 27,22 22,79
Cardiovascular and cancer mortality in Hungary
(1993-2003).
Men Women
Type of cancer 1993 2003 1993 2003
Lung 115,60 121,6 32,32 44,2
Colorectal 45,38 57,8 40,70 43,5
Mouth, lip 24,32 42,5 Not among the 6 most
significant causes
Not among the 6 most
significant causes
Prostate 25,13 27,2 --- ---
Stomach 32,35 24,6 20,87 16,0
Liver, gallbladder
17.07 18,1 21,75 17,4
Pancreas x x 12,92 16,4
Breast (female) --- --- 43,09 43,4
Cancer deaths in Hungary (per 100.000)
Cancer is a worldwide health issue
MALES
Site High Low Ratio
Population Rate Population Rate H/L
Tongue Bermuda: Black 16.3 China, Qidong U.S., Los Angeles: Filipino The Gambia
0.2 81.5
Stomach Japan, Yamagata 93.3 India, Ahmedabad 2.1 44.4
Colon U.S., Hawaii: Japanese
37.2 The Gambia 0.7 53.1
Rectum Czech., Boh.& Morav.
22.9 The Gambia 0.7 32.7
Liver Thailand, Khon Kaen China, Qidong
90.0 Netherlands, Maastricht 0.8 112.5
Pancreas U.S., California-Alameda: Black
13.7 The Gambia 0.4 34.3
Larynx Spain, Basque Country
20.4 China, Qidong 0.1 204.0
Bronchus, Lung New Zealand: Maori
119.1 The Gambia 1.0 119.1
Melanoma of Skin
Australian Capital Territory
28.9 Kuwait: Kuwaitis Thailand, Khon Kaen
0.1 289.0
Prostate U.S., Atlanta: Black 102.0 China, Qidong 0.8 127.5
Testis Switzerland, Zurich 8.8 The Gambia 0.2 44.0
Bladder Italy, Trieste 34.0 U.S., Los Angeles: FilipinoThe Gambia India, Madras
1.8 18.9
Kidney, etc. Italy, Trieste 15.5 Algeria, Sétif 0.2 77.5
All Sites Australia, Tasmania
493.8 The Gambia 59.1 8.4
FEMALES
SiteHigh Low Ratio
Population Rate Population Rate H/L
Mouth India, Bangalore 9.6 Japan, Yamagata
Spain, Tarragona
Poland, Warsaw Rural Algeria, Sétif
0.1 96.0
Esophagus India, Bangalore 8.8 U.S., Los Angeles: Japanese
0.1 88.0
Stomach Japan, Yamagata 42.9 India, Ahmedabad The Gambia
1.5 28.6
Colon Bermuda: Black 34.4 Algeria, Sétif 0.9 38.2
Rectum Israel: Born in Europe, America
16.1 The Gambia 0.6 26.8
Liver Thailand, Khon Kaen
38.3 Canada, Prince Edward Island
0.1 383.0
Bronchus, Lung
New Zealand: Maori
62.2 India, Madras 1.4 44.4
Melanoma of Skin
Australian Capital Territory
25.3 China, Qidong Kuwait: Non-Kuwaitis Algeria, Sétif
0.1 253.0
Breast U.S., California-Bay Area: White
104.2 The Gambia 3.4 30.6
All Sites Canada, British Columbia
345.4 The Gambia 39.6 8.7
•All sites 359.2 253.0 1.4
•Larynx 5.8 2.4 2.4
•Prostate 72.8 31.2 2.3
•Stomach 14.2 6.3 2.3
•Myeloma 9.2 4.5 2.0 ••Oral cavity and pharynx 8.3 4.2 2.0••Esophagus 12.9 7.2 1.8••Liver 9.2 5.9 1.6
•Lung & bronchus 109.1 79.7 1.4
•Pancreas 16.2 12.0 1.4
•Small intestine 0.7 0.5 1.4
•Colon & rectum 34.4 25.8 1.3
Cancer Sites in Which African-American Death Rates* Exceed White Death Rates* for Men, US, 1995-1999
*Per 100,000, age-adjusted to the 2000 US standard population.Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
African American White
Ratio of African American/White
Cancer Sites in Which African-American Death Rates* Exceed White Death Rates for Women, US, 1995-1999
*Per 100,000, age-adjusted to the 2000 US standard population.Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
•All sites 203.5 169.8 1.2
•Stomach 6.8 3.0 2.3
•Myeloma 6.8 3.0 2.3
•Uterine cervix 6.2 2.8 2.2
•Esophagus 3.5 1.7 2.1
•Larynx 0.9 0.5 1.8
•Uterine corpus, NOS 6.9 3.9 1.8
•Soft tissue, including heart 1.9 1.3 1.5
•Colon & rectum 25.4 18.0 1.4
•Pancreas 13.0 9.0 1.4
•Liver & intrahepatic bile duct 3.9 2.8 1.4
•Breast 37.1 28.2 1.3
•Urinary bladder 3.1 2.3 1.3
African-American
White Ratio of African American/White
• Different locations have different rates of cancer.Why does China have a 50x higher rate of liver cancer than Canada?Why does US have a 20x higher colon cancer rate than India?
• Epidemiological studies of human cancerCan't do highly controlled studies as for animals.Immigrant studies--track cancer incidence among individuals that have immigrated to country.
• Japanese women in Japan Japanese immigrants to US Rates of cancer: Rates of cancer: After one or
Stomach cancer high, two generations, develop breast cancer low cancer patterns like other US women
m
Daganat Nem Nigéria USA
1960-69 Feketék Fehérek
Vastagbél férfiak 34 349 294
Végbél férfiak 34 159 217
Máj férfiak 272 67 39
Hasnyálmirigy férfiak 55 200 126
Gége férfiak 37 236 141
Tüdő férfiak 27 1,546 983
Prosztata férfiak 134 724 318
Emlő nők 337 1,268 1,828
Méhnyak nők 559 507 249
Méhtest nők 42 235 695
Limfoszarkoma férfiak 133 10 4
Daganatincidenciák afrikai és amerikai fekete népesség körében
Daganatincidenciák japán őslakosság és hawaii bevándorlók körében
m
Hawaii, 1968-72
Daganat Nem Japán Japán Kaukázusi
Nyelőcső férfiak 150 46 75
Gyomor férfiak 1,331 397 217
Vastagbél férfiak 78 371 368
Végbél férfiak 95 297 204
Tüdő férfiak 237 379 962
Prosztata férfiak 14 154 343
Emlő nõk 335 1,221 1,869
Méhnyak nők 329 149 243
Méhtest nők 32 407 714
Petefészek nők 51 160 274
Factors Contributing to the Incidence of Human Cancer
Diet (35%)
Alcohol (3%)
Industrial Products (1%)
Tobacco (30%)
Reproductive & Sexual behavior (7%)
Occupation (4%)Infection (10%)
Food Additives (<1%)
Geophysical Factors (3%)
Pollution (2%)
Medicines (1%)
Adapted from Doll, R. and Peto, R.(1981) The Causes of Cancer. Oxford Medical Publications.
Unknown (?)
Causes of cancer
• Nutrition 35%• Smoking 30%• Infections 10%• Sexual behaviour 7%• Occupation 4%• Alcohol 3%• Geophysical factors
3%• Pollution, others 2%
0% 10% 20% 30% 40%
Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2001
Geography and occupation influence cancer risk
Urban
industrial pollutiondietary fat intakesedentary lifestyle
occupational hazards
Rural
sun exposureaccessibility of medical
caremeat consumption
**toxic chemicals from fertilizers
Stan
dard
ized
Mor
tali
ty R
ate
300
200
100
0
Stomach (M)
Japa
nese
1st g
ener
atio
n m
igra
nts
2nd
gene
rati
on m
igra
nts
US
whi
te m
ales
Breast (F)Ja
pane
se
1st g
ener
atio
n m
igra
nts
2nd
gene
rati
on m
igra
nts
US
whi
te f
emal
es
Standardized mortality ratios for breast (F) and stomach (M) cancer among Americanresidents of Japanese Ancestry and White Americans (SMR relative to rate in Japan)
Preventable
Convergence towards hostcancer rates
70-90% of Cancer is Preventable
Large influence of lifestyle and environment
Population Impact
Population Attributable Risk %
Percent of cancer cases attributable to a risk factor
= Function of exposure prevalence and increase in risk
High exposure to benzene in certain occupations increases bladder cancer risk 8 fold
Smoking associated with a 4-fold increase bladder cancer risk
Which exposure has a larger impact on the number of bladder cancers?
Major Causes of Cancer - Tobacco *
Cancer site Relative Risk PAR%
Lung 10-12 80-90%Oral 8-10 60-90%Esophogus 7-9 70-80%Bladder 4-6 40-50%Pancreas 3-5 29-34%
Most important cause of cancer
Smoking usually multiplies the background rates
* Source - Cancer Epid and Prevention, Shottenfield and Fraumeni
Major Causes of Cancer - Diet
Cancer site Diet factors PAR%*
Colorectal Fat and vegetable 60%Breast Fat and vegetable 27%Prostate Fat consumption 20%Stomach Nitrite, fruit and vegetable 70%Pancreas Sugar, vegetable 30%
* Miller - Chronic Diseases in Canada 1992
Complex to study
Risks not well understood - nutrients vs individual foods vs patterns
No single factor shows a strong and consistent relationship
Major Causes of Cancer - Viruses
Factor Cancer sites
Human Papillomaviruses (HPV) CervixHelicobacter pylori StomachHepatisus B (HBV) LiverEbstien-Barr (EBV) LymphomaHIV N-H Lymphoma, Kaposi’s sarcoma
Strong evidence for an infective etiology of childhood leukemia- pattern of occurrence tends to cluster like infectious disease
Major Causes - Reproductive and hormonal factors
Protective Factors late age at menarcheearly age at menopauseearly first childbirthhigh parity
Risk factorsOral contraceptive useEstrogen replacement therapyChemicals (PCB) which mimic estrogens
Breast cancer risk influenced by endogenous and exogenous hormones
Major Causes of Cancer - Occupation
Occupation Cancer Sites
Agricultural Leukemia, Testes, Lung
Cement Lung
Mining Lung, Stomach, Leukemia
Dry Cleaning Bladder, Kidney, Cervix, Lung
Firefighters Brain, Lung
Oil Refinery Leukemia, Bone, Brain, Kidney, Pancreas, Skin, Lymphatitc
Several occupations, and exposures within these occupations are linked to high risk for cancer
An important starting point for epidemiologic studies of specific exposures - e.g. study highly exposed populations
Major Causes of Cancer - Genetics
Factor Prevalence RR PAR
Mutations Low High LowPolymorphisms High (> 1%) Low High
Causes of Breast Cancer Prevalence RR PAR
BRCA1/BRCA2 Very low Very High 2%
Specific genetic mutations which are associated with a very high probability for developing cancer, may account for relatively few cases because they are present in a small proportion of the underlying population
Major Causes of Cancer - Gene-Environment Interactions
Polymorphism (NAT2)
Slow acetylation Fast acetylation
Bladder cancer relative risk Bladder cancer relative riskassociated with smoking = 8 associated with smoking = 1.5
Interaction - effect of smoking is different in subjects with a specific polymorphic gene
- better understanding of the effects of established carcinogens - uncover low levels of risk previously masked by genetic susceptibility
Summary
Epidemiologic evidence suggests that a substantial proportion of cancermortality and morbidity can be prevented
Lifestyle and Environmental factors play an important role- smoking- diet- hormonal- UV radiation- occupation- air and water
Risk factors for many cancer sites still poorly understood
Investigation of gene-environment interactions has enormous potential to contribute to the understanding of cancer risk
Major role for epidemiology in identifying preventable risk factors
Epidemiologic Study Designs
Experimental Intervention / Randomized Controlled Trial
Observation Cohort studyCase-Control study
Methodological considerations in observation studies
CONFOUNDING
Exposure (Exhaust) Outcome (bladder cancer)
Confounder (Smoking)
Potential confounders SmokingPhysical activityDiet
Egyes daganatok kezelésének relatív költségei
Daganat Fejlett országok (%) Fejlődő országok (%)
Tüdő 122 782
Máj 113 727
Nyelőcső 111 709
Leukémia 109 700
Gyomor 107 687
Kolorektális 105 336
Ajak-szájüreg 76 243
Emlő 65 206
Méhnyak 54 174
Átlag 100 641