Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984,...

44
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
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Transcript of Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984,...

Page 1: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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)

Page 2: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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%

Page 3: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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.)

Page 4: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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)

Page 5: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Regular Intake and Supplementation Level of -Carotene

mg/day

Page 6: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Calcium: Dietary Intake and Supplements

mg/day

Page 7: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Factors Affecting the Antioxidant/Prooxidant Properties of

-carotene

• Concentration

• Presence of certain prooxidant compounds

• Oxigene-concentration

• Presence of other antioxidants

Page 8: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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)

Page 9: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 10: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 11: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 12: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 13: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 14: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 15: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.
Page 16: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 17: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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).

Page 18: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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)

Page 19: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Cancer is a worldwide health issue

Page 20: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 21: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 22: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

•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

Page 23: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 24: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

• 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

Page 25: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.
Page 26: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 27: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 28: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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 (?)

Page 29: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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%

Page 30: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2001

Page 31: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 32: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 33: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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?

Page 34: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 35: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 36: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 37: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 38: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 39: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 40: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 41: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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

Page 42: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Epidemiologic Study Designs

Experimental Intervention / Randomized Controlled Trial

Observation Cohort studyCase-Control study

Page 43: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

Methodological considerations in observation studies

CONFOUNDING

Exposure (Exhaust) Outcome (bladder cancer)

Confounder (Smoking)

Potential confounders SmokingPhysical activityDiet

Page 44: Retrospective studies: Dietary carotenoids and lung cancer risk Ziegler et al 1984, 1986CarotenoidsDecreased (significant) Samet et al, 1985CarotenoidsDecreased.

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