Cancer Epidemiology An Introduction The Epidemiologic Perspective Aims of Cancer Epidemiology Methods of Epidemiology Historical Perspective and Examples Contemporary Studies The Future

Epidemiology “ Distribution and determinants of disease frequency in human populations” –Humans: not laboratory animals, cells –Populations: not individuals, case series –Frequency: Quantification of occurrence and risks –Distribution: Descriptive epidemiology –Determinants: Analytic epidemiology

Aims of Cancer Epidemiology Uncover new etiologic leads –study of the distribution of cancer –quantify the risk associated with different exposures and host factors Promote insights into the mechanisms of carcinogenesis Assess efficacy of preventive measures Investigate predictors of survival

Methods of Cancer Epidemiology Descriptive Studies –Incidence, mortality, survival –Time Trends –Geographic Patterns –Patterns by Age, Gender, SES, Ethnicity Analytic Studies –Case-control –Cohort

Challenges to Interpretation –Observational vs. Experimental Design –Cancer “clusters” –Study Design and Conduct Study Size Biases: Misclassification, confounding, selection –Exposure assessment important –Epidemiology and “strong” and “weak” effects –Impact on a population level –Replication critical

Cancer Epidemiology Sources US SEER Registry System IARC International Registries State/Hospital Registries Etiologic Clues –“Alert” Clinician –Experimental Studies

Cancer Epidemiology Historical Perspective 1700: Italian Physician noted breast cancer more common among nuns 1775: Percivall Pott noted scrotal cancer more common among chimney sweeps 1700s: pipes and lip cancer, snuff and nasal cancer 1842: Uterine cancer in Verona, Nuns vs. others 1800s: Occupational cancers

Cancer Epidemiology Historical Perspective Tobacco and Lung Cancer Asbestos and Lung Cancer Leather Industry and Nasal Cancer Dyes and Bladder Cancer Ionizing Radiation and Many Cancers DES and Vaginal Adenocarcinoma EBV and Burkitt’s Lymphoma HPV and Cervical Cancer

Attributable Risk Environmental5% Lifestyle45% Occupational4% Pharmacologic2% Biologic (viruses)4%

Cancer Epidemiology Current/Future Topics Infectious Agents Obesity Physical Activity Diet Hormones Immunologic Factors Inherited Susceptibility (Polymorphisms)

Cancer Epidemiology Current/Future Topics Tumor (somatic) Alterations Cancer Classification Biomarkers of Exposure/Effect Improved US Registry System Study Pooling Epidemiologic/Statistical Methods Survivorship

Andrew F. Olshan, Ph.D. Departments of Epidemiology and Otolaryngology/Head & Neck Surgery University of North Carolina Head and Neck Cancer as a Model for Gene-Environment Interaction

Epidmiology of Head and Neck Cancer Squamous Cell Carcinoma of oral cavity, pharynx, larynx One of the 10 most frequent worldwide (3 rd among males) Oral (10.1 /100,000) Males (15.1) Females (5.9) Blacks (12.3) Whites (10.0) Larynx Males (6.9) Females (1.4) Blacks (6.6) Whites (3.9) 40,100 new cases/year in US 11,800 new deaths Survival- Five-year 54% oro-pharyngeal, 65% laryngeal –Blacks (34%) Whites (56%)

SCCHN as a Model System KNOWN Risk Factors Molecular Markers – Tumor Suppressor Genes – Oncogenes – Virus Other Characteristics – Preneoplastic lesions – Recurrence/second primaries

Exposure Internal Dose Agent or Metabolites Biologically Effective Dose DNA Adducts Preclinical Biologic Effect Mutation Oncogenes Tumor Suppressor Preneoplastic Lesions CLINICALDISEASE SUSCEPTIBILITY Genetic/Metabolic DNA Repair Nutritional Status Immunologic Status

Tobacco and Alcohol Alcohol Drinks/Wk From Blot 88

Research Question –Do polymorphisms of activation, detoxification, and DNA repair genes confer a differential risk of head and neck cancer in individuals with exposure to tobacco and alcohol?

Carolina Head And Neck CancEr Study Population-Based NC Study –46 Counties (Central/Eastern NC) –Rapid Case Ascertainment (1-2 months) –Physician Consent –1,700 cases (4 yrs) Whites (1330), blacks (402), <50yrs (225) Oral (779), Pharynx (364), Larynx (589)

46 County Study Area

CHANCE STUDY –DMV Controls –Phone number search, letter, phone call –Frequency Matched (age, race, gender)

CHANCE STUDY –In-person interview Demographics Smoking/Alcohol Hx Diet (74 items NCI DHQ) Oral Health Medical Hx Screening Hx Family Hx of Cancer –Blood Draw (3 tubes) or Mouth rinse –Genotyping (HTG)- Taqman method

CHANCE Study TARGET GENES –CYP1A1 CYP1B1 CYP2C9 CYP2E1 –NAT1 GSTM1 GSTT1 GSTP1 –EPHX1 NQO1 MPO MnSOD –ADH2 ADH3 ADH4 –AGT XRCC1 APE1 HOGG1 –XPD

CHANCE Study Tumor Blocks Tumor expression arrays Medical Records Social Factors Access to Health Care Screening Follow-up of Cases (new survivor study)