Bibliography (www.mcgill.ca/cancerepi/courses/cancerbio/): Franco - - PDF document

Module: Epidemiology of Neoplasia Course: Biology of Cancer #516-504A

• Dr. Eduardo L. Franco, Professor and Director, Division of Cancer Epidemiology

Departments of Oncology and Epidemiology, McGill University eduardo.franco@mcgill.ca, 398-6032, http://www.epi.mcgill.ca/franco/

Objectives of this lecture: Overview of cancer burden Worldwide distribution Time trends in North America Measuring risk factors Concept of relative risk and attributable proportion Tobacco and lung cancer as a paradigm Basis for cancer prevention Research and public health framework Achievable goals

Bibliography (www.mcgill.ca/cancerepi/courses/cancerbio/): Franco EL. Epidemiology in the study of cancer. In: Bertino JR et al. (eds.), Encyclopedia of Cancer, Vol.

• 1. Academic Press, San Diego, 1997 (pp. 621-641).

Franco EL, Rohan TE (eds.) Cancer Precursors: Epidemiology, Detection, and Prevention. Springer- Verlag, New York, 2002, 430 pages, ISBN 0-387- 95188-1 Copies of the slides Supplemental material in the website above

http://www.mcgill.ca/cancerepi/courses/cancerbio/

Adapted from: Ruddon, 1995

5 15 20 25 10 103 106 109 1012 Years Number of cancer cells

1 mg 1 g 1 kg

Dormant phase of tumor growth Rapid tumor progression phase

Vascularization Clinical detection Lethal tumor burden Invasion

Estimated numbers of new cancer cases and deaths in 2002 (Parkin et al., CA Cancer J Clin 2005) Estimated numbers of new cancer cases and deaths in 2002 (Parkin et al., CA Cancer J Clin 2005)

ASIR (x 100,000), All sites except skin non-melanoma; top 10 and bottom 10 countries, Males

(Source: Globocan 2002)

50 100 150 200 250 300 350 400 450

USA Hungary New Zealand Belgium Australia France Luxembourg Croatia Czech Republic Switzerland Liberia Fiji Guinea-Bissau Senegal Mauritania Cape Verde Vanuatu Gambia Niger Congo Brazzaville

ASIR (x 100,000), All sites except skin non-melanoma; top 10 and bottom 10 countries, Females

50 100 150 200 250 300 350

USA Israel New Zealand Denmark Iceland Australia Canada United Kingdom Norway Luxembourg Turkey Algeria Congo Brazzaville Morocco Libya Sudan Egypt Tunisia Oman Gambia (Source: Globocan 2002)

ASIR (x 100,000), Liver carcinoma; top 10 and bottom 10 countries, Males

20 40 60 80 100 120

Mongolia Mozambique Korea Gambia Rwanda Cameroon Thailand China Guinea Senegal Iran Morocco Guyana Bangladesh Sri Lanka Suriname Iraq Syria Algeria Lebanon (Source: Globocan 2002)

Age-adjusted death rate (per 100,000 men)

Year

Age-adjusted death rates in the US (2000 population); Source: American Cancer Society, Surveillance Research

10 20 30 40 50 60 70 80 90 100 1930 1940 1950 1960 1970 1980 1990 2000

Colorectal Liver Lung Pancreas Prostate Stomach

Age-adjusted death rate (per 100,000 women)

Year

Age-adjusted death rates in the US (2000 population); Source: American Cancer Society, Surveillance Research

10 20 30 40 50 60 70 80 90 100 1930 1940 1950 1960 1970 1980 1990 2000

Breast Colorectal Lung Ovary Pancreas Stomach Uterus

Canada: Incidence rates among men (age-adjusted to the 1991 Canadian population)

Source: Canadian Cancer Statistics 2006 + previous ones

25 50 75 100 125 150 1 9 6 9 1 9 7 1 1 9 7 3 1 9 7 5 1 9 7 7 1 9 7 9 1 9 8 1 1 9 8 3 1 9 8 5 1 9 8 7 1 9 8 9 1 9 9 1 1 9 9 3 1 9 9 5 1 9 9 7 1 9 9 9 2 1 2 3 2 5

Year Age-adjusted rate (per 100,000)

Prostate Lung Colorectal Melanoma Stomach NHL

Canada: Incidence rates among women (age-adjusted to the 1991 Canadian population)

Source: Canadian Cancer Statistics 2006 + previous ones

20 40 60 80 100 120 1 9 6 9 1 9 7 1 1 9 7 3 1 9 7 5 1 9 7 7 1 9 7 9 1 9 8 1 1 9 8 3 1 9 8 5 1 9 8 7 1 9 8 9 1 9 9 1 1 9 9 3 1 9 9 5 1 9 9 7 1 9 9 9 2 1 2 3 2 5 Year Age-adjusted rate (per 100,000) Breast Lung Colorectal Endometrium Ovary Cervix

Incidence and mortality rates in children 0-14 years All sites of cancer - US SEER program 1973-2002 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 1972 1977 1982 1987 1992 1997 2002 Year Age-adjusted Rate (x100,000)

APPROACHES TO CARCINOGENICITY EVALUATION

EXPERIMENTAL OR MECHANISTIC

• In vitro short-term genotoxicity assays
• In vivo animal studies
• Structure-activity relationships

EPIDEMIOLOGICAL Observational (non-inferential)

• Case reports

Observational (inference at the population level)

• Surveillance of incidence and mortality trends
• Ecologic (correlation or aggregate) studies

Observational (inference at the level of the individual)

• Cross-sectional studies
• Case-control studies
• Cohort studies

Experimental

• Intervention trials
• Clinical trials

AR for some established causal relations in cancer

Attributable Proportion Prevalence of risk factor

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 20% 40% 60% 80% 100%

1.5 2 10 20 50 100 5

HPV and cervical cancer Smoking and lung cancer HBV and liver cancer Sunburn and melanoma Alcohol and oral cancer

Franco & Harper, Vaccine 2005

• 2 - 1

<1 Food additives <1 - 2 <1 Industrial products <1- 2 <1 Medicines <1 - 2 <1 Pollution 0.5 - 1 1 UV light 2 - 4 3 Alcohol 2 - 8 3 Occupation 2 - 8 5 Heredity 4 - 8 6 Ionizing radiation 5 - 10 7 Reproductive factors and hormones 10 - 25 18 Infection: viral, bacterial, parasitic 20 - 60 30 Diet 25 - 40 33 Tobacco Plausible Range (%) Best estimate (%) Factor

Sources: Doll & Peto, 1981; 1996; Levine et al, 1989; Li et al., 1991; Pisani et al., 1997; Key et al., 1997; Parkin et al., 2006

Proportion of cancers attributed to different factors

Risks of male cigarette smokers for dying from lung cancer relative to nonsmokers, in some major cohort studies.

Country

• No. of

subjects in study Daily no. of cigarettes Relative risk* Reference USA 440 558 1.0 Hammond (1966) 1-9 4.6 10-19 7.5 20-39 13.1 ≥ 40 16.6 Japan 122 261 1.0 Hirayama (1974) 1-9 1.9 10-14 3.5 15-24 4.1 25-49 4.6 ≥ 50 5.7 Sweden 27 342 1.0 Cederlöf et al (1975) 1-7 2.1 8-15 8.0 ≥ 16 12.6 UK 34 440 1.0 Doll & Peto (1976) 1-14 7.8 15-24 12.7 ≥ 25 25.1

* Ratio between the occurrence rate of cancer among smokers and that

among nonsmokers. Source: Tomatis et al, 1990.

Lung cancer mortality ratios (RR) in ex-smokers of cigarettes, by number of years since stopping smokinga (Muir et al, 1990)

Study population Time since stopping smoking (years) RR Reference British doctors 1-4 16.0 Doll & Peto (1976); 5-9 5.9 Doll et al. (1980) 10-14 5.3 ≥ 15 2.0 Current smoker 14.0 US veteransb 1-4 18.8 Rogot & Murray (1980) 5-9 7.7 10-14 4.7 15-19 4.8 ≥ 20 2.1 Current smoker 11.3 Japanese men 1-4 4.7 Hirayama (1975) 5-9 2.5 ≥ 10 1.4 Current smoker 3.8 Men aged 50 – 69 years in 25 US states (1-19 cigs/day) < 1 1-4 5-9 > 10 Current smoker 7.2 4.6 1.0 0.4 6.5 Hammond et al. (1977) Men aged 50 – 69 years in 25 US states (> 20 cigs/day) < 1 1-4 5-9 > 10 Current smoker 29.1 12.0 7.2 1.1 13.7 Hammond et al. (1977)

Cancer Prevention Levels of Intervention

Level Public health goal Research goal Intervention Primary control incidence identify risk factors lifestyle, environmental Secondary control prevalence identify early signs, precursors screening Tertiary improve outcome identify prognostic factors management, follow-up Quaternary improve QOL, minimize suffering identify determinants of pain, disability palliative care IARC estimates of theoretical reduction in cancer risk to be achieved by primary prevention (1)

Cancer site Preventive measure Reduction in incidence or mortality Region Lung eliminate tobacco smoking control of occupational exposures reduction of air pollution 60 - 90% 10% uncertain worldwide W.nations urban areas Stomach increase consumption of fresh vegetables and fruits up to 50% worldwide Breast reduce dietary fat/animal protein weight reduction for the obese uncertain 10% worldwide Colorectal reduce dietary fat/animal protein+ increase vegetable consumption up to 35% Western nations Cervix control of STDs use of barrier contraceptives eliminate tobacco smoking reduce high parity 50% uncertain uncertain 30% worldwide worldwide W.nations developing countries Oral eliminate tobacco smoking + chewing eliminate tobacco smoking+ reduce alcohol consumption avoidance of salted fish (NPC) 60 - 80% 60 - 80% 10 - 90% Asia W.nations China Adapted from: Tomatis et al., 1990