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McGill University Department of Epidemiology & Biostatistics Summer Session - 2008 Cancer Epidemiology and Prevention Course EPIB 671 Course Coordinator: Eduardo L. Franco, Professor Departments of Epidemiology & Biostatistics and Oncology Director, Cancer Epidemiology Unit (514-398-6032)

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McGill University Department of Epidemiology & Biostatistics Summer Session - 2008


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    1. McGill University Department of Epidemiology & Biostatistics Summer Session - 2008 Cancer Epidemiology and Prevention Course EPIB 671 Course Coordinator: Eduardo L. Franco, Professor Departments of Epidemiology & Biostatistics and Oncology Director, Cancer Epidemiology Unit (514-398-6032) E-mail: eduardo.franco@mcgill.ca

    2. Course EPIB 671: CANCER EPIDEMIOLOGY AND PREVENTION - 2008 Department of Epidemiology & Biostatistics, McGill University Eduardo Franco (514-398-6032, eduardo.franco@mcgill.ca) http://www.mcgill.ca/cancerepi/courses/caepisum/

    3. EPIB 671 (Summer Session) Files to download for students registered in EPIB 671 Course Description and Bibliography: general information about the course, its contents and bibliography (not essential in class but be sure to read before coming to class on Monday)EPIB671_CourseSchedule2007 [.pdf]CourseDescriptionSummer2007 [.pdf] Entire set of transparencies to be used by Dr. Franco(needed in class to facilitate note-taking)Slides-EPIB671-2007 [.pdf] or,Slides-EPIB671-2007-condensed_BW [.pdf] IARC-Monographs-Evaluation Summaries: Appendix material (Not essential but will be frequently alluded to in class)IARC_Monographs [.pdf] TaubesScience269-164s and TaubesLetters: Article by Taubes, Science 1995 and associated letters to the editor (Please read it. It will be discussed in class)TaubesScience269-164s [.pdf] JNCI85-958: Article by Schiffman et al., JNCI 1993 (Please read it. It will be discussed in class)JNCI85-958 [.pdf] Gorey-AJPH-1997: Article by Gorey et al., AJPH 1997 (Please read it. It will be discussed in class)Gorey-AJPH-199 [.pdf] Chapter5-Franco&Rohan: Chapter 5 of Franco & Rohan textbook on the epidemiology of cancer precursors. Contains supplemental information concerning etiologic models and measurement error (Not essential in class but if you have a chance read it before the session on methods, specially if you have not taken an intermediate level epidemiology course)Chapter5-Franco-Rohan.pdf [.pdf] CaDetPrev-26-350: Review article by Franco et al., 2002. Contains detailed information concerning guidelines for cancer screening and prevention (Not essential. Useful as reference material to supplement the discussion during the session on screening and prevention)CaDetPrev-26-350 [.pdf] Chapter by Franco in the Encyclopedia of Cancer 1997: Contains an overview of cancer epidemiology and prevention. Its contents reflect the general layout of the course (Not essential but supplements the discussion on general applications of epidemiology in cancer research)EncyclopCancerChapter [.pdf] Review article by Franco et al., Sem Cancer Biol 2004 on causal relations in cancerSemCaBiol-14-413-2004.pdf [.pdf] Giovannucci-NEJM-1995: Article by Giovannucci et al., NEJM 1995 (Please read it. It will be discussed in class)Giovanucci-NEJM [.pdf] Franco-JCE.pdf: Article by Franco et al., JCE 1993. (Please read it. It will be discussed in class).FrancoJCE [.pdf] OccupationalCancer.ppt: Occupational Cancer Lecture by Dr. GoldbergGoldberg's Lecture 2007 [.ppt] Dr. Ghadirian's Lecture 2007: Nutrition and Cancer Lecture by Dr. Ghadirian.Ghadirian's Lecture_2007 [.pdf] Summary of incidence ratesGlobocan_2002_All_sites_Incidence [.pdf] Article by Kyzas et al., JNCI 2005 (will be discussed in class).JNCI_Kyzas_97_1043_2005 [.pdf] Article by Eaker et al. and Commentary by Franco, PLoS-Medicine 2006:PLoS-Med-Eaker-3-321-2006 [.pdf]PLoS-Med-Franco-3-e48-2006 [.pdf]

    4. Expanded Purview of Cancer Epidemiology • Cancer surveillance: burden of disease, incidence and mortality trends, cancer clusters • Cancer risk: assessing candidate etiologic factors • Cancer prevention: assessing the validity and the impact of chemoprevention and other preventive approaches • Cancer screening: assessing efficacy, comparing competing technologies • Cancer survival: assessing prognostic factors, determinants of quality of life in terminally ill patients

    5. Milestones in Cancer Epidemiology • Establishment of first tumour registries (1935, 1943) and development of data quality standards by the IARC and IACR (1970’s) • Doll & Hill (1950); Wynder & Graham (1950): case-control approach to study cancer causes (cigarettes and lung cancer) • Surgeon General's Report on tobacco and cancer (1964) • WHO's IARC founded in 1965; major contributions: CI5C and carcinogenicity monograph series • Doll & Peto’s report to the US OTA (1981) • Emergence of molecular epidemiology (late 80's) • Launching of mega-studies of screening (60's - 80's) and diet (80's) • Focus on precursor lesions as opposed to clinically invasive cancer (90’s) • Studies of SNPs and genome-wide association studies (2000’s)

    6. Age-adjusted rates of death from lung cancer in relation to smoking and asbestos exposure Using a multiplicative scale: Smoking: 11.2 Asbestos: 5.3 Expected RR with no independent effects: 11.2 x 5.3 = 59.4 Using an additive scale: Smoking: (11.2 – 1) x 100 = 1010% Asbestos: (5.3 – 1) x 100 = 430% Expected with no independent effects: 1440% or equivalently, RR=15.4 Adapted from Hammond et al., 1979; Beaglehole et al. 1993

    7. Caretaker Genes Gatekeeper Genes DNA repair Carcinogen metabolism Cell cycle control Programmed cell death Shields and Harris, 2000

    8. From: Cavenee, 1995

    9. Cancer causation: the Darwinian process Mel Greaves Lancet Oncol 2002; 3: 244–51 “Clonal evolution of a cancer. All cancers evolve by Darwinian principles: clonal proliferation, genetic diversification within the clone, and selective pressure enabling mutant subclones to bridge the bottlenecks (such as anoxia, restricted space and nutrients, apoptosis imposition). Each colour in the figure represents a cell (and its descendent clone) acquiring the first (blue) or additional, sequential mutations. Grey represents dying cells. This diagram greatly simplifies the extensive genetic diversity, complex population structure, and highly variable dynamics of cancer clones. N, normal stem cells.”

    10. 1012 1 kg Invasion 109 1 g Number of cancer cells 106 1 mg 103 5 10 15 20 25 Years Clinical detection Lethal tumor burden Vascularization Dormant phase of tumor growth Rapid tumor progression phase Adapted from: Ruddon, 1995

    11. Non-epidemiologic approaches used in assessing the evidence concerning the carcinogenicity of a suspected chemical, physical, or biological exposure or its circumstances (Adapted from Franco et al., SCB 2004) * Other supporting in vivo and in vitro data relevant to evaluation of carcinogenicity can also be used, particularly if they provide insights into mechanisms of absorption, metabolism, DNA binding or repair, hormonally-mediated effects, genetic damage, altered cell growth, loss of euploidy, cytopathic changes, and related biological effects.

    12. Epidemiologic approaches used in assessing the evidence concerning the carcinogenicity of a suspected chemical, physical, or biological exposure or its circumstances (Adapted from Franco et al., SCB 2004) ** RCTs may target communities or providers as units of randomly allocated intervention. However, this is done for convenience of study design; in practical terms inference is at the individual level.

    13. Coverage of IARC’s “Cancer Incidence in Five Continents” Monographs

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

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

    16. Age structure of developing and developed countries Male Female Developing Developed Proportion (%) Source: IARC, 2000

    17. Effect of Choice of Standard Population for Age-adjustment Average age-adjusted incidence rates per 100,000 (1998-2002) in the US SEER program

    18. ASIR (x 100,000), All sites except skin non-melanoma; top 10 and bottom 10 countries, Males (Source: Globocan 2002)

    19. ASIR (x 100,000), All sites except skin non-melanoma; top 10 and bottom 10 countries, Females (Source: Globocan 2002)

    20. ASIR (x 100,000), Liver carcinoma; top 10 and bottom 10 countries, Males (Source: Globocan 2002)

    21. ASIR (x 100,000), Cervical cancer; top 10 and bottom 10 countries (Source: Globocan 2002)

    22. Age-adjusted death rate (per 100,000 men) Year Age-adjusted death rates in the US (2000 population); Source: American Cancer Society, Surveillance Research

    23. Age-adjusted death rate (per 100,000 women) Year Age-adjusted death rates in the US (2000 population); Source: American Cancer Society, Surveillance Research

    24. Age-standardized (2000 US population) incidence rates in areas covered by the US NCI’s SEER program. Source: Ries et al., 2008 and previous reports

    25. Age-standardized (2000 US population) incidence rates in areas covered by the US NCI’s SEER program. Source: Ries et al., 2008 and previous reports

    26. Canada: Incidence rates among men (age-adjusted to the 1991 Canadian population) Source: Canadian Cancer Statistics 2008 + previous ones

    27. Canada: Incidence rates among women (age-adjusted to the 1991 Canadian population) Source: Canadian Cancer Statistics 2006 + previous ones

    28. From: Armstrong and Mann, 1985

    29. Design Layout of a Cohort Study From: Beaglehole et al., W.H.O., 1993

    30. Design Layout of a Case-Control Study From: Beaglehole et al., W.H.O., 1993

    31. Components of Etiologic Models in Cancer: Commonly Suspected Relations V1 and V2= candidate risk factor variables 1 and 2 O= cancer outcome Adapted from Franco et al., 2002

    32. Components of Etiologic Models in Cancer: Less Suspected Mechanisms V1 and V2= candidate risk factor variables 1 and 2 O= cancer outcome Adapted from Franco et al., 2002

    33. Case-control study Cohort study Effect of measurement error in epidemiologic studies Parameter: RR (exp-dis) Assumptions: P(exp)=20%, P(dis)~2.5% Adapted from: Franco and Rohan, 2002

    34. Relative risks for associations between HPV and cervical cancer in case-control studies of first generation NAH: non-amplified DNA hybridization PCR: polymerase chain reaction

    35. Cumulative incidence of SIL among women with a normal Pap smear at entry(Local cytology) HPV positive HPV negative Ludwig-McGill Cohort (August 1997)

    36. Cumulative incidence of SIL among women with a normal Pap smear at entry(Review cytology) HPV positive HPV negative Ludwig-McGill Cohort (August 1997)

    37. Features of Epidemiologic Study Designs Modified from: Beaglehole et al. 1993