ONCOLOGY Epidemiology

1LungBreastLung1,037,000 2StomachColon/rectumStomach798,000 3Colon/rectumCervix uteriBreast796,000 4ProstateStomachColon/rectum783,000 5LiverLungLiver437,000 6Mouth/pharynxOvaryProstate396,000 7EsophagusCorpus uteriCervix uteri371,000 8BladderLiverMouth/pharynx363,000 9LeukemiaMouth/pharynxEsophagus316,000 10NHL*EsophagusBladder261,000 Total New RankMalesFemalesBoth SexesCases *Non-Hodgkin’s lymphoma. Adapted from Parkin DM, et al. CA Cancer J Clin. 1999;49:39. Leading cancers worldwide

ONCOLOGY Epidemiology 1N. America369.9N. America Australia/N.Z.312.7Australia/N.Z W. Europe294.8N. Europe Japan270.9S. America* N. Europe270.0W. Europe E. Europe269.4Micronesia/205.2 Polynesia 7S. Europe256.0Southern Africa S. America*255.1Melanesia Southern Africa247.4S. America † Eastern Asia ‡ 235.7Central America180.1 Incidence/Incidence/ Rank Region100,000 Region100,000 *Temperate South America. † Tropical South America. ‡ Other than Japan or China. Adapted from Parkin DM, et al. CA Cancer J Clin. 1999;49:43. Cancer incidence by world region MalesFemales

ONCOLOGY Epidemiology Adapted from Greenlee RT, et al. CA Cancer J Clin. 2001:51; Leading causes of death in 2001 Percentage of Total Deaths, US Heart Diseases Cancer Cerebrovascular Diseases Chronic Obstructive Lung Diseases Accidents Pneumonia & Influenza Diabetes Mellitus Suicide Nephritis Cirrhosis of the Liver

ONCOLOGY Epidemiology Evolution of cancer death rates, males Year Pancreas Lung & Bronchus Prostate Stomach Colon & Rectum Leukemia Liver Rate per 100,000 Male Population Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

ONCOLOGY Epidemiology Evolution of cancer death rates, females Year Uterus Stomach Pancreas Ovary Lung & Bronchus Colon & Rectum Breast Rate per 100,000 Female Population Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

ONCOLOGY Epidemiology *Other nervous system. † Non-Hodgkin’s lymphoma. Mortality for leading cancers in 2001 Adapted from Greenlee RT, et al. CA Cancer J Clin. 2001;51: Males by Age (years), US All Ages Lung & bronchus 91,399 Prostate 32,203 Colon & rectum 28,024 Pancreas 13,806 NHL 12, Leukemia 663 Brain & ONS* 627 NHL † 612 Lung & bronchus 484 Colon & rectum Lung & bronchus 59,377 Prostate 15,742 Colon & rectum 15,615 Pancreas 8,070 NHL 6,341 > 80 Lung & bronchus 16,011 Prostate 15,373 Colon & rectum 7,455 Bladder 3,034 Pancreas 2, Lung & bronchus 15,521 Colon & rectum 4,539 Pancreas 2,671 NHL 2,399 Esophagus 2,141

ONCOLOGY Epidemiology *Other nervous system. † Non-Hodgkin’s lymphoma. Mortality for leading cancers in 2001 Greenlee RT, et al. CA Cancer J Clin. 2000;50: All Ages Lung & bronchus 63,075 Breast 41,737 Colon & rectum 28,950 Pancreas 14,529 Ovary 13, Breast 1,604 Uterine cervix 634 Leukemia 456 Lung & bronchus 442 Brain & ONS* Lung & bronchus 39,077 Breast 18,292 Colon & rectum 12,950 Pancreas 7,454 Ovary 7,038 > 80 Lung & bronchus 13,392 Colon & rectum 12,174 Breast 9,949 Pancreas 5,193 NHL † 3, Breast 11,889 Lung & bronchus 10,155 Colon & rectum 3,472 Ovary 2,841 Pancreas 1,775 Females by Age (years), US

ONCOLOGY Epidemiology Male cancer statistics Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;51:18, Estimated incidenceEstimated deaths Melanoma of skin Oral cavity & pharynx Lung & bronchus Pancreas Kidney Colon & rectum Prostate Urinary bladder Leukemia Non-Hodgkin’s lymphoma All others 5% 3% 14% 2% 3% 10% 31% 6% 3% 5% 18% Esophagus Lung & bronchus Pancreas Liver Kidney Colon & rectum Prostate Urinary bladder Leukemia Non-Hodgkin’s lymphoma All others 3% 31% 5% 3% 10% 11% 3% 4% 5% 22%

ONCOLOGY Epidemiology Female cancer statistics Adapted from Greenlee RT, et al. CA Cancer J Clin. 2001;51:18, % 15% 25% 6% 2% 11% 5% 2% 5% 4% 23% Melanoma of skin Thyroid Breast Lung & bronchus Pancreas Colon & rectum Ovary Uterine corpus Urinary bladder Non-Hodgkin’s lymphoma All others 4% 2% 31% 13% 2% 11% 4% 6% 2% 4% 21% Brain Breast Lung & bronchus Pancreas Stomach Colon & rectum Ovary Uterine corpus Non-Hodgkin’s lymphoma Leukemia All others Estimated incidenceEstimated deaths

ONCOLOGY Epidemiology Environmental factors Occupational exposure Lifestyle factors Biologic agents Pharmacologic/Iatrogenic factors Known cancer causes Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Cancer of the esophagus Head and neck cancer Liver cancer Breast cancer Alcohol-related cancers Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001; Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Major cause Lung Larynx Oral cavity Esophagus Contributory factor Pancreas Bladder Kidney Stomach Uterine cervix Smoking-related cancers Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Agents Hepatitis B Hepatitis C HIV-1 HTLV-1 HPV Epstein-Barr Virus-related cancers Site of Cancer Liver Kaposi’s sarcoma Adult T-cell lymphoma Uterine cervix Burkitt’s lymphoma, nasopharynx, Hodgkin’s disease Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Agents Helicobacter pylori Schistosoma haematobium Opisthorchis viverrini Bacterial-related cancers Site of Cancer Stomach Urinary bladder Liver Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Pharmacologic/iatrogenic contributors Ullrich RL, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001; Agent Ionizing radiation Type of Cancer Breast cancer Leukemia Skin cancer Thyroid cancer Lung cancer

ONCOLOGY Epidemiology Pharmaceuticals AgentsSite of Cancer Cancer chemotherapeutic drugsBone marrow Immunosuppressive drugsReticuloendothelial system Exogenous hormones Nonsteroidal estrogensVagina, breast, testis Steroidal estrogensEndometrium Oral contraceptivesLiver, endometrium TamoxifenEndometrium Phenacetin analgesicsKidney, pelvis, bladder Pharmacologic/iatrogenic contributors (cont’d) Adapted from Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Selected Industries Associated with Exposure to Carcinogens IndustryCarcinogenCancer Shipbuilding, demolition, insulationAsbestosLung, pleura, skin Varnish, glueBenzeneLeukemia Pesticides, smeltingArsenicLung, skin, liver Mineral refining and manufacturingNickel, chromiumLung, nasal passages Furniture manufacturingWood dustsNasal passages Petroleum productsPolycyclic hydrocarbonsLung Rubber manufacturingAromatic aminesBladder Vinyl chlorideVinyl chlorideLiver RadiumRadiumLung, bone Outdoor occupationsUltraviolet lightSkin Occupational-related cancers Costanza ME, et al. American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;55-74.

ONCOLOGY Epidemiology Germline tumor suppressor gene inactivation Germline oncogene activation DNA repair defects Ecogenetic traits Abnormal tissue architecture Humoral tumor promoters and regressors Genetic risk factors: mechanisms of cancer predisposition Bale AE, Brown SJ. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Family history of cancer Cancer appears earlier in life Multiple and bilateral tumors May include rare tumor types (eg, retinoblastoma) Multisystem involvement Genetic risk factors: characteristics of cancer families Bale AE, Brown SJ. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

ONCOLOGY Epidemiology Familial Cancer SyndromeSite of Cancer Neurofibromatosis type 1 CNS, neurofibrosarcomas, pheochromocytomas, leukemia Neurofibromatosis type 2CNS, spine von Hippel-Lindau diseaseCNS, renal cell, spine, pancreas, adrenal glands Li-Fraumeni syndromeCNS, breast, head and neck, soft tissue, osteosarcoma, adrenal cortical carcinomas, leukemia Wilms’ tumor geneWilms’ tumor Basal cell carcinoma syndromeSkin, CNS, ovary Genetic risk factors: Familial cancer syndromes Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997; Linehan WM, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;

ONCOLOGY Epidemiology Familial Cancer SyndromeSite of Cancer Familial adenomatous polyposis coliColorectal, jaw, skull, skin, stomach, CNS Hereditary nonpolyposis colorectal Colorectal cancer Cowden’s syndromeThyroid, stomach, breast, ovary BRCA-1Breast, ovary BRCA-2Breast (female and male) Genetic risk factors: Familial cancer syndromes (cont’d) Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997; Safai B. Cancer: Principles & Practice of Oncology. 5th ed. 1997; Cohen AM, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997; Dickson RB, Lippman ME. Cancer: Principles & Practice of Oncology. 5th ed. 1997;

Reducing mortality Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995; The National Cancer Institute estimates that cancer mortality rates could be significantly reduced, as follows: ONCOLOGY Epidemiology 8% to 16% by a 15% decrease in tobacco use among adults 8% by dietary measures (ie, reduction of dietary fat to <25% and double dietary fiber) 3% by early screening and early detection 10% to 26% by the wider application of state-of- the art treatments

Risk reduction Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995; ONCOLOGY Epidemiology Relative risk = risk of developing a disease in the population exposed to a risk factor, divided by the risk of developing that same disease among those not exposed to that same risk factor Population attributable risk = the percentage by which the disease could be eliminated if exposure to the risk factor was eliminated

ONCOLOGY Epidemiology Site of Relative Attributable CancerRisk FactorRiskRisk Lung LungCigarette smokingStrong 87% OccupationStrong13% Residential radon exposureModerate10% Second-hand smokeWeak2% Diet low in beta caroteneWeak- Dietary fat/low-vegetable dietPossible5% Urban air pollutionPossible- Colorectal ColorectalHigh-fat/low-vegetable dietWeak50% Physical inactivityWeak20% OccupationWeak- ObesityWeak- Modifiable risk factors Adapted from Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;44.

ONCOLOGY Epidemiology Site of Relative Attributable CancerRisk FactorRiskRisk Breast BreastFirst full-term pregnancy after age 30Moderate7% Large doses of chest radiationModerate2% Never marriedWeak- Never having childrenWeak5% Post-menopausal obesityWeak12% Alcohol consumptionWeak- High fatPossible- Low physical activityPossible- Use of diethylstilbestrolPossible- Use of oral contraceptives or ERTPossible- Modifiable risk factors (cont’d) Adapted from Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;45.

ONCOLOGY Epidemiology Site of Relative Attributable CancerRisk FactorRiskRisk Cervix CervixMultiple sex partnersModerate38% Early age at first intercourseModerate25% History of STDModerate5% Cigarette smokingWeak32% Use of barrier contraceptivesWeak- Low dietary intake of vitamin A, Weak- beta-carotene, and folate Modifiable risk factors (cont’d) Adapted from Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;45.

ONCOLOGY Epidemiology Test/ProcedureSexAgeFrequency Colorectal cancer screeningM&F>50Annual FOBT, flexible sigmoidoscopy every 5 years, or both; colonoscopy every 10 years; or double-contrast barium enema every 5 years PSA test + digital rectal examM>50Every year if life expectancy > 10 years Pap testF>18*Every year, if normal >3 times, Pap test may be performed less frequently at discretion of physician Pelvic examF>18*Every year Breast self-examF>20Every month Breast clinical examF20-39Every 3 years >40Every year MammographyF>40Every year Health counseling and cancer M&F20-39Every 3 years checkups>40Every year ACS Screening Recommendations for Colorectal, Prostate, Cervical, and Breast Cancer Adapted from Smith RA, et al. CA Cancer J Clin 2001;51: Asymptomatic People (Average Risk) * Or before if sexually active. † At menopause, for women at high risk for endometrial cancer due to history of infertility, obesity, failure to ovulate, abnormal uterine bleeding, unopposed ERT or tamoxifen use.