National Institute of Health Includes many institutes….

1. Epidemiology and OncologyTranslational Research in Clinical OncologyOctober 15, 2012Neil Caporaso, MDGenetic Epidemiology Branch,Division of Cancer Epidemiology and Genetics, National Cancer Institute

2. NIHNational Cancer Institute Division of Cancer Epidemiology and Genetics Genetic Epidemiology Branch National Institute of Health Includes many institutes…. We are INTRAMURAL ~ 85% $$ are extramural Cancer ETIOLOGY Other Branches focus on Nutrition, Hormones, Infection, Occupation, Statistics, Radiation

3. A Population Perspective on Cancer1. Introductory concepts2. Tools Epidemiologists use 3. Accomplishments of Epidemiology4. Challenges of Epidemiology5. Futures of Epidemiology

4. A Population Perspective on Cancer1. Introductory concepts2. Tools Epidemiologists use 3. Accomplishments of Epidemiology4. Challenges of Epidemiology5. Futures of Epidemiology

5. Domain of epidemiologyEpidemiology = causes of health and disease in human populations = epi (upon) + demos (the people) + logia (talk about)An OBSERVATIONAL science (like astronomy, evolutionary biology)Contrast with experimentalInvestigator does NOT get to pick who is exposed or unexposed Free-living people make choices about participating…possible BIASStudy of individuals with and without disease (contrast with Clinical Research)

6. What are the goals of epidemiology ?1. Identify the causes of cancer2. Quantify risks3. Identify risk groups4. Understand mechanisms5. Public health and health services6. Identify syndromes

7. Observational vs. ExperimentalEpidemiologists are ethically prohibited fromdoing experiments on people So, we observe large populations and seehow their outcomes relate to what people do (i.e., smoke, drink, eat, etc.)The weakness of the ‘observational’ argument was used by tobacco companiesto deny evidence linking cigarettes and cancer……

8. Epidemiologists emphasize preventionRationale:Effective (think polio, smallpox, smoking cessation, clean water, HPV…)Cheap (compared to late stage interventions)Public health orientationEliminate disease at the sourceDownsidesOften requires time to demonstrate effectiveness Less dramatic than treatmentHarder to see all the disease you have preventedLess positive political impactFewer Nobel PrizesPrimary = directed to susceptibility stageExample: Needle exchange to prevent AIDS, HPV vaccineSecondary = directed to subclinical stageExample: Screen for cervical cancer with Pap SmearTertiary = directed to clinical stage

9. Epidemiologists worry about biasBias= systematic deviation from truthIf the participation rate in a study is lowThe study subjects may not be REPRESENTATIVE of the target populationsand the worry is the study results may not be GENERALIZABLE to the general populationSelection Bias = subjects in the study are ‘selected’ and therefore nonrepresentative

10. Pilot studies: participation rate 30% participate in phone survey.49% participated in Invitation letter, Follow-up by phone, In hospital, Advertisements, Cash award, Physicians’ letter and Home/hospital 73% participate in New interviewers, Physicians’ call, Gas coupon, TV ads, New invitation letter, Mayor’s letter and Toll-free phone lineTotal number of subjects in pilot investigations: 156 Cases - 212 Controls 30% 73% 49%

11. Epidemiologists worry about controlsDownsidesOften requires time to demonstrate effectiveness Less dramatic than treatmentHarder to see all the disease you have preventedLess positive political impactFewer Nobel PrizesPrimary = directed to susceptibility stageExample: Needle exchange to prevent AIDS, HPV vaccineSecondary = directed to subclinical stageExample: Screen for cervical cancer with Pap SmearTertiary = directed to clinical stageExample: Treat diabetic retinopathy to prevent blindness

12. Why Population Controls? Gold standardRepresentative of the population from which cases deriveCan calculate absolute ratesReduces selection biasIMPLIESDefined population in time and spaceSpecified eligibility and exclusion criteriaDefined and high response rate

13. Epidemiologist as consultantQuestions the consulting epidemiologist will ask:Your study design is…?Your controls came from….?Did you collect key covariate data?Did you consider bias, confounding?What was the original hypothesis? (data dredging)Are you underpowered?Did you validate your marker?Epidemiologist is helpful when a question involves the population (as opposed to an individual, organ, cell, etc.)

14. The most common question epidemiologists get!Can you explain why…………..My grandmother smoked all her life. she drank heavily, her exercise was the TV remote,she never used a seat belt, she had bacon and buttered toast for breakfast…She drank shots on her 90th birthdayAnd she outlived all her doctors….. The race is not to the swift or the battle to the strong, nor does food come to the wise or wealth to the brilliant or favor to the learned; but time and chance happen to them all. (Ecclesiastes)Deterministic vs. Probabilistic

15. A Population Perspective on CancerIntroductory ConceptsTools Epidemiologists’ UseAccomplishments of EpidemiologyChallenges of EpidemiologyFutures for Epidemiology

16. ToolsMapsRegistries (SEER)Methods Example: Causation

17. Cancer mortality map

18. GIS Geographic patterns of disease and exposure via satellite. Examples, used to estimate nitrate, pesticide levels

19. SEER Surveillance, Epidemiology, and End Results (SEER) Program26% of US populationincidence and survival, patient demographics, primary tumor site, tumor morphology and stage at diagnosis, first course of treatment, and follow-up for vital status comprehensive source of population-based information

20. SEER

21. Cancer Incidence Rates*, All Sites Combined, All Races, 1975-2000 Rate Per 100,000 Men Both Sexes Women

22. Men cancer rates 75% increase due to PSA screening

23. Cancer Incidence Rates* for Women, US, 1975-2000 Rate Per 100,000 Breast Colon & rectum Lung Uterine corpus Ovary *Age-adjusted to the 1970 US standard population. Source: Surveillance, Epidemiology, and End Results Program, 1973-1998, Division of Cancer Control and Population Sciences, National Cancer Institute, 2001.

24. Cancer incidence rates

25. Cancer death rates Why are cancer death rates leveling off?

26. Lung cancer death rates …..because the most common cause of cancer death is declining……

27. Men cancer death rates

28. Women cancer death rates

29. Children and cancer

30. Childhood Cancers (< 14 ys)Incidence 8,600 new cases/yr 12,400 (0 – 19 ys) Mortality 1,500 deaths/yr 2,300 (0 – 19 ys) rates  50% since 1973 Etiology -- poorly understood

31. Cancer in men

32. Cancer in women

33. How do you prove a cause?1. It should confer high risk2. It should be consistent3. Dose response 4. Cause occurs first5. Biology makes sense

34. Lung cancer increases with cigarette smoking

35. Smoking leads to lung cancer

36. Squamous tumors

37. Basal cell carcinoma

38. Lung cancer and smoking cessation

39. A Population Perspective on CancerIntroductory ConceptsTools Epidemiologists’ UseAccomplishments of EpidemiologyChallenges of EpidemiologyFutures for Epidemiology

40. Accomplishments (highly selected!)Identification of the Specific Causes of cancerRole as advocates of public healthRole as advocates of preventionIdentification of tobacco as causal factor for lung cancerRole of secondary tobacco smokeRole in the molecular redefinition of cancer

41. What are the general risk factors for cancer?Increasing ageEnvironmental factorsGenetic factorsCombinations of the above!

42. Causes of Cancer Deaths* Environmental pollution, Infectious agents, Lifestyle, Alcohol use, Occupational factors, Medicine, Radiation, Genetic susceptibility, other & unknown causes Tobacco ~30-35% Diet ~ 30-35% Other* ~30-35%

43. Most Cancer is due to the EnvironmentDramatic differences in cancer rates by geography and over time areonly compatible with extrinsic environmental causesEstablished by a vast body of descriptive, ecological, and analytical epidemiology

44. International Variation in Cancer RatesType of cancer H/L highest lowestMelanoma 155 Australia JapanNasopharynx 100 Hong Kong UKProstate 70 US (Blacks) ChinaLiver 50 China CanadaCervix 28 Brazil IsraelStomach 22 Japan KuwaitLung 19 US (Blacks) IndiaColon 19 US (Whites) IndiaBladder 16 Switzerland IndiaPancreas 11 US (Blacks) IndiaOvary 8 Maori (NZ) KuwaitBreast 7 Hawaii IsraelLeukemia 5 Canada India

45. Lung cancer mortality rate in Xuan Wei is among the highest in China County-specific female lung cancer mortality rates (per 100,000, 1973-75)

46. Indoor Air Pollution in China

47. Copper smelter, Montana Copper Smelter, Montana

48. Skull With Cigarettevan Gogh

49. Tobacco and public health major cause of preventable morbidity & mortality 1/5 US deaths (450,000 USA, 3M world/y) 10 million tobacco deaths/yr (2030, WHO) 30% of all cancer, 8 sites, all difficult to treat tobacco related disease costs Medicare/ Medicaid > $10B/yr each In spite of widespread knowledge of the health consequences of smoking - rates in US adolescents are stable or increasing - declines in adults- leveled off - individual smoking cessation difficult

50. Per-Capita Consumption of Different Forms of Tobacco in The U.S. 1880-2003 Data Source USDA