Module: Epidemiology of Neoplasia Course: Biology of Cancer #516-504A D r. 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/ 10 12 1 kg Number of cancer cells Invasion 10 9 1 g 10 6 1 mg 10 3 5 10 15 20 25 Years Clinical Lethal tumor Vascularization detection burden Dormant phase of Rapid tumor tumor growth progression phase Adapted from: Ruddon, 1995
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 0 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 (Source: Globocan 2002) ASIR (x 100,000), All sites except skin non-melanoma; top 10 and bottom 10 countries, Females 0 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 0 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) 100 Colorectal Liver 90 Age-adjusted death rate (per 100,000 men) Lung Pancreas 80 Prostate Stomach 70 60 50 40 30 20 10 0 1930 1940 1950 1960 1970 1980 1990 2000 Year Age-adjusted death rates in the US (2000 population); Source: American Cancer Society, Surveillance Research
100 Breast Colorectal Age-adjusted death rate (per 100,000 women) 90 Lung Ovary 80 Pancreas Stomach 70 Uterus 60 50 40 30 20 10 0 1930 1940 1950 1960 1970 1980 1990 2000 Year Age-adjusted death rates in the US (2000 population); Source: American Cancer Society, Surveillance Research Canada: Incidence rates among men (age-adjusted to the 1991 Canadian population) 150 Prostate Lung Colorectal Melanoma 125 Stomach NHL Age-adjusted rate (per 100,000) 100 75 50 25 0 9 1 3 5 7 9 1 3 5 7 9 1 3 5 7 9 1 3 5 6 7 7 7 7 7 8 8 8 8 8 9 9 9 9 9 0 0 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 Year Source: Canadian Cancer Statistics 2006 + previous ones
Canada: Incidence rates among women (age-adjusted to the 1991 Canadian population) 120 Breast Lung Colorectal Endometrium 100 Ovary Cervix Age-adjusted rate (per 100,000) 80 60 40 20 0 9 1 3 5 7 9 1 3 5 7 9 1 3 5 7 9 1 3 5 6 7 7 7 7 7 8 8 8 8 8 9 9 9 9 9 0 0 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 Year Source: Canadian Cancer Statistics 2006 + previous ones
Incidence and mortality rates in children 0-14 years All sites of cancer - US SEER program 1973-2002 16.0 14.0 Age-adjusted Rate (x100,000) 12.0 10.0 8.0 6.0 4.0 2.0 0.0 1972 1977 1982 1987 1992 1997 2002 Year 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 100% 100 HPV and cervical cancer 90% 20 Attributable Proportion 50 Smoking and lung cancer 80% 10 70% 60% HBV and liver cancer 50% Alcohol and oral cancer 5 40% Sunburn and melanoma 30% 2 20% 1.5 10% 0% 0% 20% 40% 60% 80% 100% Prevalence of risk factor Franco & Harper, Vaccine 2005 Proportion of cancers attributed to different factors Best estimate Plausible Factor (%) Range (%) Tobacco 33 25 - 40 Diet 30 20 - 60 Infection: viral, bacterial, parasitic 18 10 - 25 Reproductive factors and hormones 7 5 - 10 Ionizing radiation 6 4 - 8 Heredity 5 2 - 8 Occupation 3 2 - 8 Alcohol 3 2 - 4 UV light 1 0.5 - 1 Pollution <1 <1 - 2 Medicines <1 <1- 2 Industrial products <1 <1 - 2 Food additives <1 -2 - 1 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
Risks of male cigarette smokers for dying from lung cancer relative to nonsmokers, in some major cohort studies. Country No. of Daily no. of Relative Reference risk * subjects in cigarettes study USA 440 558 0 1.0 Hammond (1966) 1-9 4.6 10-19 7.5 20-39 13.1 ≥ 40 16.6 Japan 122 261 0 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 0 1.0 Cederlöf et al (1975) 1-7 2.1 8-15 8.0 ≥ 16 12.6 UK 34 440 0 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 smoking a (Muir et al, 1990) Study population Time since RR Reference stopping smoking (years) 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 veterans b 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 < 1 7.2 Hammond et al . (1977) years in 25 US states 1-4 4.6 (1-19 cigs/day) 5-9 1.0 > 10 0.4 Current smoker 6.5 Men aged 50 – 69 < 1 29.1 Hammond et al . (1977) years in 25 US states 1-4 12.0 (> 20 cigs/day) 5-9 7.2 > 10 1.1 Current smoker 13.7
Cancer Prevention Levels of Intervention Level Public health Research goal Intervention goal control incidence identify risk factors lifestyle, Primary environmental control prevalence identify early signs, screening Secondary precursors Tertiary improve outcome identify prognostic management, factors follow-up Quaternary improve QOL, identify palliative care minimize suffering determinants of pain, disability IARC estimates of theoretical reduction in cancer risk to be achieved by primary prevention (1) Reduction in Cancer site Preventive measure incidence or Region mortality Lung eliminate tobacco smoking 60 - 90% worldwide control of occupational exposures 10% W.nations reduction of air pollution uncertain urban areas Stomach increase consumption of fresh up to 50% worldwide vegetables and fruits Breast reduce dietary fat/animal protein uncertain worldwide weight reduction for the obese 10% Colorectal reduce dietary fat/animal protein+ up to 35% Western increase vegetable consumption nations Cervix control of STDs 50% worldwide use of barrier contraceptives uncertain worldwide eliminate tobacco smoking uncertain W.nations reduce high parity 30% developing countries Oral eliminate tobacco smoking + 60 - 80% Asia chewing eliminate tobacco smoking+ reduce alcohol 60 - 80% W.nations consumption avoidance of salted fish (NPC) 10 - 90% China Adapted from: Tomatis et al., 1990
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