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Cancer Epidemiology part II


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Cancer Epidemiology, Risk factors for most common types, mortality, prevention and yeild of cancer prevention. gender, geography, infections, tobacco, environmental riskk factors.

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Cancer Epidemiology part II

  1. 1. Cancer Epidemiology II Professor Tarek Tawfik Amin
  2. 2. The Major Cancers Lung (ICD-10 C33 and C34) Breast (female, C50) Colon/rectum (C18-C20) Stomach (C16) Prostate (C61) Liver (C22) Cervix uteri (C53) Esophagus (C15)
  3. 3. Percentage of Cancer Deaths Attributed to Various Factors (Doll R and Peto R, JNCI, 1981) Tobacco Use: 30% (25%-40%) Diet: 35% (10%-70%) Infection: 10%? (1%-?) Reproductive & Sexual Behavior: 7% (1%- 13%) Occupation: 4% (<2%-8%) Alcohol: 3% (2%-4%) Geophysical factors (natural radiation): 3% (2- 4%) Pollution: 2% (<1% – 5%) Food additive: <1% (-
  4. 4. Harvard Center for Cancer Prevention ( Tobacco: 30% Diet in adult life, including obesity: 30% Sedentary lifestyle: 5% Infectious agents: 5% Defects in single genes that run in family: 5-10%
  5. 5. Chemical/environmental carcinogens Smoking and lung cancer Sun exposure and squamous cell carcinoma of skin Asbestos exposure and lung cancer Smoked food risk with nitrosamines and adenocarcinoma of the stomach Alcohol drinking and squamous
  6. 6. Radiation Exposure to ultraviolet radiation (in the form of sunlight) and squamous cell carcinoma of skin Ionizing radiation is related to skin cancer and leukemia in radiologist
  7. 7. Viral factors HPV (human papilloma virus) and Cervix cancer EBV(Epstein-Barr virus) and Nasopharyngeal cancer, Burkitt’s lymphoma HBV (hepatitis B virus) and hepatocellular carcinoma
  8. 8. Geographical risk
  9. 9. Table 2.5 part 1 of 2Table 2.5 part 1 of 2 The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007)
  10. 10. Specific Cancer Incidence and Migratory Patterns: Cancers and Environmental Effects
  11. 11. One canOne can distinguishdistinguish genetic fromgenetic from environmentalenvironmental and culturaland cultural features infeatures in cancercancer causation bycausation by analyzinganalyzing populationspopulations with similarwith similar geneticgenetic backgroundsbackgrounds living inliving in differentdifferent environments.environments.
  12. 12. Epidemiological Datacan also sometimesprovide cluesabout thebiological mechanismsunderlying certain typesof cancers. Malignant Melanoma(Solar radiation exposure) Burkitt’sLymphoma(Co-infection with virus transmitted by mosquitoesalso transmitting malaria)
  13. 13. Cancer Incidenceand Changesin GeneExpression: Reciprocal Translocation - 9 to 22 Reciprocal Translocation: Chronic Myelogenous Leukemia (CML) - 8 to 14 Reciprocal Translocation: Burkitts Lymphoma
  14. 14. oReciprocal translocation between chromosomes 9 and 22 produces fusion of a cancer-inducing gene, the abelson or abl gene with information on another chromosome. oThis chromosome fusion is expressed as a fusion protein involving the abl gene product. oThis miss-expressed fusion protein drives cell division in leucocytes leading to chronic myelogenous leukemia.
  15. 15.  Figure 4.13aFigure 4.13a The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007) p. 109p. 109 Reciprocal Translocation (8 to 14) in Burkitt’s LymphomaReciprocal Translocation (8 to 14) in Burkitt’s Lymphoma
  16. 16. Figure 4.12Figure 4.12 The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007) Incidence of Burkitt’s Lymphoma in Relation to Infectious Disease Etiology:Incidence of Burkitt’s Lymphoma in Relation to Infectious Disease Etiology: Aedes simpsoni mosquito transmission vector for malariaAedes simpsoni mosquito transmission vector for malaria and Epstein Barr Virus co-infectionand Epstein Barr Virus co-infection
  17. 17. Epidemiology of Cancer Based on AgeEpidemiology of Cancer Based on Age
  18. 18. AgeEffctAgeEffct IncidenceIncidence
  19. 19. Incidence of Various Kinds of Cancers in Men and Women as a Function ofIncidence of Various Kinds of Cancers in Men and Women as a Function of AgeAge
  20. 20. Environmental and Occupational Cancers Effects from Nuclear Plant Melt-Down
  21. 21. WorkCxWorkCx
  22. 22. Table 2.7Table 2.7 The Biology of CancerThe Biology of Cancer (© Garland Science 2007)(© Garland Science 2007)
  23. 23. Journal of the National CancerJournal of the National Cancer Institute, July, 1996Institute, July, 1996 Chernobyl nuclearChernobyl nuclear power-plant melt-down,power-plant melt-down, April 1986April 1986 Environmental radiation from the Chernobyl Nuclear Plant Melt-down produced a marked increase in Thyroid cancers in children with a delay of about five years. Fortunately, thyroid cancers can be managed fairly successfully and respond to treatment. This, of course, presupposes that modern treatment is available to the children. This supposition may not be correct in some, or even in many cases.
  24. 24. Cultural Associations and Specific Cancers
  25. 25. Journal of the National Cancer InstituteJournal of the National Cancer Institute October, 1996October, 1996 A specific histological type of cancer, such as stomach cancer, can have markedly different incidence rates within different ethnic/cultural groups within a larger society. This points to cultural and possibly to genetic differences that may contribute to the differences in incidence rate. In the case of stomach cancer in different cultural/ethnic groups within the U.S., one contributing factor has been related to differences in cooking practices, including the use of charcoal in cooking. However, recent evidence concerning endemic infections with different types of Helicobacter Pylori that resides in the stomach in large numbers of people around the world suggests that there may be interactions between strains of H. Pylori and the genetic backgrounds of individuals that affect the risk of developing stomach and esophageal cancers.
  26. 26. 0 1000 2000 3000 4000 5000 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 YEAR NumberofCigarettes 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 1st 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 1st Surgeon General’s Report 1st World Conference on Smoking and Health Broadcast Ad Ban 1st Great American Smoke-out OTC Nicotine Medications Master Settlement Agreement Great Depression
  27. 27. Tobacco Use in the US, 1900-2005 0 500 1000 1500 2000 2500 3000 3500 4000 4500 5000 1900 1905 1910 1915 1920 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 Year PerCapitaCigaretteConsumption 0 10 20 30 40 50 60 70 80 90 100 Age-AdjustedLungCancerDeath Rates* *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. Per capita cigarettePer capita cigarette consumptionconsumption Male lung cancerMale lung cancer death ratedeath rate Female lungFemale lung cancer death ratecancer death rate
  28. 28. Men Women 0 10 20 30 40 50 60 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 YEAR %CURRENTSMOKERS 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 or some days. 24.5% 18.8%
  29. 29. Smoking and Other Cancers Head and neck cancers (oral, laryngeal and pharyngeal cancers) Esophageal cancer Stomach cancer Pancreatic Cancer Bladder cancer Cervical cancer Liver cancer
  30. 30. Environmental Tobacco Smoke 3,000 nonsmoking Americans die of lung cancer 300,000 children suffer from lower respiratory tract infections.
  31. 31. Obesity and Cancer
  32. 32. Obesity, globally International Association for the Study of Obesity estimated in 2007 ~40-50% of men and 25%-35% of women in EU were overweight (25-29.9 kg/m2 ) Additional 15-25% of men and women were obese. WHO’s in 2005: Globally, ~ 1.6 billion adults (age 15+) were overweight; at least 400 million adults were obese. Projects that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese. At least 20 million children under the age of 5 years are overweight globally in 2005. Not just a problem in high income countries
  33. 33. BMI and Mortality ProspectiveStudiesCollaboration, Lancet,2009
  34. 34. Renehan,2008
  35. 35. van Kruijsdijk RCM C, CEBP, 2009  Potential pathways linking obesity with cancer
  36. 36. IGF and Insulin pathway Calle EE, Kaaks R. Nature, 2004
  37. 37. Breast cancer, overview Most common cancer among females 192,370 estimated newly incident female cases, 2009 40,170 estimated female deaths, 2009 Survival rate by stage ~96% among localized ~84% for regional ~27% for distant  African-American women younger than 50 years of age have a higher age- specific incidence than White women Risk Factors Age Genetics Race Hormones Nulliparity, late age of parity, early menarche. Obesity Benign breast disease Diet Alcohol Smoking? Gale Model  ktool/
  38. 38. Renehan, 2008
  39. 39. Breast Cancer and Obesity summary In general, BMI and body weight is positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer Weight gain has also been associated with greater risk of post-menopausal breast cancer. This effect may be modified by HRT use. Implicated pathways include: Estrogen IGF-1 Inverse relationship found in premenopausal women may be a result of lower circulating sex steroid hormones.
  40. 40. Colon Cancer, overview Third most common cancer among men and women 106,100 estimated cases for 2009 49,920 estimated deaths 5-year survival rate: 90% localized 68% regional 11% distant African Americans and Ashkenazi Jews have one of the highest incidences Risk factors Age Colon polyps Genetics Race/ethnicity History of bowel disease Obesity Diet Alcohol Smoking Type 2 Diabetes
  41. 41. Obesity and colorectal cancers, summary In 2002-03 IARC concluded there is sufficient evidence that obesity is associated with an increased risk in colo-rectal cancer. This relationship is stronger among men than women. Possibly because body weight and fat distribution differs between men and women. Evidence in rectal cancer is inconclusive. Potential pathways: Hyperinsulemia IGF-1 Adipokines and hormones.
  42. 42. Prostate Cancer, overview Most common cancer among men. 192,280 estimated cases for 2009 27,360 estimated deaths for 2009 Average 5 year survival rate: ~over 99% localized and regional ~32% distant African-American men are also more likely to be diagnosed at an advanced stage Risk Factors Age Lifetime probability of prostate cancer 1 in 6 Race Geographical region Family History Genetics (8q24) Diet? Obesity? Infection? Smoking?
  43. 43. Infections-Associated Malignancies
  44. 44. 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) Cervical cancer (human papilloma virus) Liver cancer (hepatitis B and C viruses) Burkitt’s lymphoma and nasopharyngeal cancer (Epstein- Barr virus) Kaposi sarcoma and Non-Hodgkin lymphoma (HIV/HHV-8) Bladder and colon cancer (schistosomiasis) Adult T-cell leukemia/lymphoma (human T-cell lymphotropic virus type I)
  45. 45. Mechanisms Chronic Inflammation and Carcinogenesis Chronic host-pathogen interaction Immunosuppression Chronic inflammation Oxidative Stress DNA damage and mutations Cell injury Cell division Infection inducing Cell proliferation Production of Oncogenic Proteins Genomic Instability from Viral Genomic Integration
  46. 46. Cancers attributable to infections worldwide, 2002 Source: Parkin, 2006Source: Parkin, 2006
  47. 47. Alcohol
  48. 48. 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 6363
  49. 49. Particulate matter
  50. 50. Polluted Water
  51. 51.  S Lippman, Cancer Res. 2009 Jul 1;69(13):5269-84S Lippman, Cancer Res. 2009 Jul 1;69(13):5269-84
  52. 52. Known risk factors Smoking causes most cancers in smokers. Among non-smokers, most cancers are of unknown cause. Infection causes most cancers in the lowest-income countries.
  53. 53. Avoidable Known Cancer Risks USA
  54. 54. Proven Cancer Prevention Strategies: Compelling non-RCT Evidence Risk Factor Avoidance Smoking prevention/cessation counseling Worker exposure reduction (asbestos, etc.) Immunization Hepatitis B HPV Screening Cervical PAP testing
  55. 55. Proven Cancer Prevention Strategies: RCT Evidence Screening Mammography with Clinical Breast Exam Fecal Occult Blood Test (colorectal cancer)
  56. 56. BRIDGING THE GAP BETWEEN CANCER TREATMENT AND PREVENTION (William WN, et al, Nat Rev Drug Discov. 2009 Mar;8(3):213-25.)
  57. 57. Widely-Accepted Prevention Strategies Insufficient or Negative Evidence Oral cancer screening examination PSA testing for prostate cancer Lung cancer screening with CT or X ray Dietary change: More vegetables and fruits Dietary change: Less fat Dietary antioxidant supplements Weight loss and exercise Sun avoidance: skin cancer
  58. 58. Deaths/year can be prevented? Tobacco Control Screening Infection Control
  59. 59. I- Tobacco-Caused Cancers – 1.15 million deaths Lung 75% of 1,300,000 deaths Oropharynx 40% of 320,000 deaths Other sites 15% of 350,000 deaths
  60. 60. II- Screen-detectable cancers – 660,000 deaths Colorectal 50% of 620,000 deaths Cervix 90% of 230,000 deaths Breast 30% of 475,000 deaths
  61. 61. III- Infection-related Cancers – 750,000 deaths Liver (immunization) 40% of 600,000 deaths Stomach (antibiotics) 60%? of 850,000 deaths [Cervix (immunization)] 50% of 230,000 deaths]
  62. 62. Overall yield of cancer prevention:: Tobacco programs 1,115,000 at low cost Infection Control 750,000 at low/moderate 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
  63. 63. Thank you