1. Cancer Epidemiology and Cancer Prevention Epidemiology 242 December 2, 2009

5. Age Standardized Incidence Rates (/100,000) USChinaWorld SiteMalesFemalesMalesFemalesMalesFemales Stomach7.23.341.419.222.010.3 Lung61.936.142.419.035.512.1 Liver5.52.037.914.215.75.8 Esophagus4.91.327.412.011.54.7 Colon/Rectum44.633.113.69.220.114.6 Breast─101.1─18.7─37.5 Leukemia11.27.4 5.7 4.15.94.1 Pancreas8.36.33.92.64.63.3 Cervix07.706.8016.2 Brain6.54.53.92.83.72.6 Prostate124.801.6025.30 Source: GLOBOCAN 2002

7. The Major Cancers Lung (ICD-10 C33 and C34) Lung (ICD-10 C33 and C34) Breast (female, C50) Breast (female, C50) Colon/rectum (C18-C20) Colon/rectum (C18-C20) Stomach (C16) Stomach (C16) Prostate (C61) Prostate (C61) Liver (C22) Liver (C22) Cervix uteri (C53) Cervix uteri (C53) Esophagus (C15) Esophagus (C15)

10. 2009 Estimated US Cancer Cases* *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2009. Source: American Cancer Society, 2009. Men 766,130 Men 766,130 Women 713,220 Women 713,220 27%Breast 27%Breast 14%Lung & bronchus 14%Lung & bronchus 10%Colon & rectum 10%Colon & rectum 6%Uterine corpus 6%Uterine corpus 4%Non-Hodgkin lymphoma 4%Non-Hodgkin lymphoma 4%Melanoma of skin 4%Melanoma of skin 4% Thyroid 4% Thyroid 3%Kidney & renal pelvis 3%Kidney & renal pelvis 3%Ovary 3%Ovary 3%Pancreas 3%Pancreas 22%All Other Sites 22%All Other Sites Prostate25% Prostate25% Lung & bronchus15% Lung & bronchus15% Colon & rectum10% Colon & rectum10% Urinary bladder7% Urinary bladder7% Melanoma of skin5% Melanoma of skin5% Non-Hodgkin5% lymphoma Non-Hodgkin5% lymphoma Kidney & renal pelvis5% Kidney & renal pelvis5% Leukemia 3% Leukemia 3% Oral cavity3% Oral cavity3% Pancreas3% Pancreas3% All Other Sites19% All Other Sites19%

11. 2009 Estimated US Cancer Deaths* ONS=Other nervous system. ONS=Other nervous system. Source: American Cancer Society, 2009. Source: American Cancer Society, 2009. Men 292,540 Men 292,540 Women 269,800 Women 269,800 26%Lung & bronchus 26%Lung & bronchus 15%Breast 15%Breast 9%Colon & rectum 9%Colon & rectum 6%Pancreas 6%Pancreas 5%Ovary 5%Ovary 4%Non-Hodgkin lymphoma 4%Non-Hodgkin lymphoma 3%Leukemia 3%Leukemia 3%Uterine corpus 3%Uterine corpus 2% Liver & intrahepatic bile duct 2% Liver & intrahepatic bile duct 2%Brain/ONS 2%Brain/ONS 25% All other sites 25% All other sites Lung & bronchus30% Lung & bronchus30% Prostate9% Prostate9% Colon & rectum 9% Colon & rectum 9% Pancreas6% Pancreas6% Leukemia4% Leukemia4% Liver & intrahepatic4% bile duct Liver & intrahepatic4% bile duct Esophagus4% Esophagus4% Urinary bladder3% Urinary bladder3% Non-Hodgkin 3% lymphoma Non-Hodgkin 3% lymphoma Kidney & renal pelvis3% Kidney & renal pelvis3% All other sites 25% All other sites 25%

12. Cigarette Smoking and Cancer Risk

13. Adult Per Capita Cigarette Consumption and Major Smoking and Health Events – United States, 1900-2001 Source: United States Department of Agriculture End of WW II 1 st Smoking-Cancer Concern Fairness Doctrine Messages on TV and Radio Non-Smokers Rights Movement Begins Federal Cigarette Tax Doubles Surgeon General’s Report on ETS 1 st Surgeon General’s Report 1 st World Conference on Smoking and Health Broadcast Ad Ban 1 st Great American Smoke-out OTC Nicotine Medications Master Settlement Agreement Great Depression

14. Tobacco Use in the US, 1900-2005 *Age-adjusted to 2000 US standard population. *Age-adjusted to 2000 US standard population. Source: Death rates: US Mortality Data, 1960-2005, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006. Cigarette consumption: US Department of Agriculture, 1900-2007. Source: Death rates: US Mortality Data, 1960-2005, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006. Cigarette consumption: US Department of Agriculture, 1900-2007. Per capita cigarette consumption Per capita cigarette consumption Male lung cancer death rate Male lung cancer death rate Female lung cancer death rate Female lung cancer death rate

16. Men Women Trends in cigarette smoking* among adults aged >18 years, by sex - United States, 1955-2002 Source: 1955 Current Population Survey; 1965-2002 National Health Interview Survey; 2002 estimates for first quarter only *Before 1992, current smokers were defined as persons who reported having smoked >100 cigarettes and who currently smoked. Since 1992, current smokers were defined as persons who reported having smoked >100 cigarettes during their lifetime and who reported now smoking every day day or some days. 24.5% 18.8%

18. Smoking and Other Cancers Head and neck cancers (oral, laryngeal and pharyngeal cancers) Head and neck cancers (oral, laryngeal and pharyngeal cancers) Esophageal cancer Esophageal cancer Stomach cancer Stomach cancer Pancreatic Cancer Pancreatic Cancer Bladder cancer Bladder cancer Cervical cancer Cervical cancer Liver cancer Liver cancer

20. Environmental Tobacco Smoke 3,000 nonsmoking Americans die of lung cancer 3,000 nonsmoking Americans die of lung cancer 300,000 children suffer from lower respiratory tract infections. 300,000 children suffer from lower respiratory tract infections.

28. Major Infection-Associated Malignancies In 2002, 17.8% of the global cancer burden (1.9 million cases) were infection-attributable Malignancy (infection) Stomach cancer (Helicobactor pylori) Stomach cancer (Helicobactor pylori) Cervical cancer (human papillomavirus) Cervical cancer (human papillomavirus) Liver cancer (hepatitis B and C viruses) Liver cancer (hepatitis B and C viruses) Burkitt’s lymphoma and nasopharyngeal cancer (Epstein-Barr virus) Burkitt’s lymphoma and nasopharyngeal cancer (Epstein-Barr virus) Kaposi sarcoma and Non-Hodgkin lymphoma (HIV/HHV-8) Kaposi sarcoma and Non-Hodgkin lymphoma (HIV/HHV-8) Bladder and colon cancer (schistosomiasis) Bladder and colon cancer (schistosomiasis) Adult T-cell leukemia/lymphoma (human T-cell lymphotropic virus type I) Adult T-cell leukemia/lymphoma (human T-cell lymphotropic virus type I)

29. Mechanisms of Infection-Induced Malignancy Chronic Inflammation and Carcinogenesis Chronic host-pathogen interaction Chronic host-pathogen interactionImmunosuppression Chronic inflammation Chronic inflammation Oxidative Stress DNA damage and mutations Cell injury Cell division Infection inducing Cell proliferation Infection inducing Cell proliferation Production of Oncogenic Proteins Genomic Instability from Viral Genomic Integration

30. Cancers attributable to infections worldwide, 2002 Source: Parkin, 2006 Source: Parkin, 2006

31. 31 9 Possible Mechanisms How Alcohol Intake Increase Cancer Risk According to Blot et al (1992) 9 Possible Mechanisms How Alcohol Intake Increase Cancer Risk According to Blot et al (1992) 1. Contain congeners and other contaminants that may be carcinogenic 2. Generated metabolites that are carcinogenic to humans 3. Act as solvent, increasing penetration of other carcinogens into target tissue 4. Reduce intake and bioavailability of nutrition 5. Inhibit the detoxification of carcinogenic compounds 6. Catalyze the metabolic activation of some compounds into carcinogens 7. Affect hormonal status 8. Increase cellular exposure to oxidants 9. Suppress immune function

32. 32 What is “ a Drink ” ? Despite the differences in concentration, the average intake of ethanol per drink is approximately constant across beverage types. Despite the differences in concentration, the average intake of ethanol per drink is approximately constant across beverage types. A standard drink is: A standard drink is: One 12-ounce bottle of beer* or wine coolerOne 12-ounce bottle of beer* or wine cooler One 5-ounce glass of wineOne 5-ounce glass of wine 1.5 ounces of 80-proof + distilled spirits.1.5 ounces of 80-proof + distilled spirits. * Different beers have different alcohol content. Malt liquor has a higher alcohol content than most other brewed beverages. * Different beers have different alcohol content. Malt liquor has a higher alcohol content than most other brewed beverages. + 80-proof== 40% ABV (alcohol by volume) + 80-proof== 40% ABV (alcohol by volume)

38. Cancer Prevention

39. S Lippman, Cancer Res. 2009 Jul 1;69(13):5269-84 S Lippman, Cancer Res. 2009 Jul 1;69(13):5269-84

40. Known risk factors Smoking causes most cancers in smokers. Smoking causes most cancers in smokers. Among non-smokers, most cancers are of unknown cause. Among non-smokers, most cancers are of unknown cause. Infection causes most cancers in the lowest-income countries. Infection causes most cancers in the lowest-income countries.

41. Avoidable Known Cancer Risks USA

42. Proven Cancer Prevention Strategies Compelling non-RCT Evidence Risk Factor Avoidance Risk Factor Avoidance Smoking prevention/cessation counseling Worker exposure reduction (asbestos, etc.) Immunization Immunization Hepatitis B HPV Screening Screening Cervical PAP testing

43. Proven Cancer Prevention Strategies RCT Evidence Screening Screening Mammography with Clinical Breast Exam Fecal Occult Blood Test (colorectal cancer)

44. BRIDGING THE GAP BETWEEN CANCER TREATMENT AND PREVENTION BRIDGING THE GAP BETWEEN CANCER TREATMENT AND PREVENTION (William WN, et al, Nat Rev Drug Discov. 2009 Mar;8(3):213-25.) (William WN, et al, Nat Rev Drug Discov. 2009 Mar;8(3):213-25.)

45. Widely-Accepted Prevention Strategies Insufficient or Negative Evidence Oral cancer screening examination Oral cancer screening examination PSA testing for prostate cancer PSA testing for prostate cancer Lung cancer screening with CT or Xray Lung cancer screening with CT or Xray Dietary change: More vegetables and fruits Dietary change: More vegetables and fruits Dietary change: Less fat Dietary change: Less fat Dietary antioxidant supplements Dietary antioxidant supplements Weight loss and exercise Weight loss and exercise Sun avoidance: skin cancer Sun avoidance: skin cancer

46. How Many Cancer Deaths/Yr Could we Prevent Now? Tobacco Control Tobacco Control Screening Screening Infection Control Infection Control

47. How Many Cancer Deaths/Yr Could we Prevent Now? Tobacco-Caused Cancers – 1.15 million deaths Lung75% of 1,300,000 deaths Lung75% of 1,300,000 deaths Oropharynx40% of 320,000 deaths Other sites15% of 350,000 deaths

48. How Many Cancer Deaths/Yr Could we Prevent Now? Screen-detectable cancers – 660,000 deaths Colorectal50% of 620,000 deaths Cervix90% of 230,000 deaths Breast30% of 475,000 deaths

49. How Many Cancer Deaths/Yr Could we Prevent Now? Infection-related Cancers – 750,000 deaths Liver (immunization)40% of 600,000 deaths Liver (immunization)40% of 600,000 deaths Stomach (antibiotics)60%? of 850,000 deaths Stomach (antibiotics)60%? of 850,000 deaths [Cervix (immunization)]50% of 230,000 deaths] [Cervix (immunization)]50% of 230,000 deaths]

50. How Many Cancer Deaths/Year Could we Prevent Now? Tobacco programs 1,115,000 at low cost Tobacco programs 1,115,000 at low cost Infection Control750,000 at low/moderate cost Infection Control750,000 at low/moderate cost Screening 660,000 at low/very high cost Screening 660,000 at low/very high cost Total deaths preventable: about 2.5 Million of the 7.5 million deaths/year from cancer worldwide