Cancer EpidemiologyAn 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 EpidemiologySources

• US SEER Registry System

• IARC International Registries

• State/Hospital Registries

• Etiologic Clues– “Alert” Clinician– Experimental Studies

Cancer EpidemiologyHistorical 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 EpidemiologyHistorical 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

• Environmental 5%

• Lifestyle 45%

• Occupational 4%

• Pharmacologic 2%

• Biologic (viruses) 4%

Cancer EpidemiologyCurrent/Future Topics

• Infectious Agents• Obesity• Physical Activity• Diet• Hormones• Immunologic Factors• Inherited Susceptibility (Polymorphisms)

Cancer EpidemiologyCurrent/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 (3rd 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

ExposureExposure

Internal Dose

Agentor Metabolites

BiologicallyEffective Dose

DNA AdductsDNA Adducts

PreclinicalBiologicEffect

MutationMutation Oncogenes Tumor Suppressor

PreneoplasticLesions

CLINICAL CLINICAL DISEASEDISEASE

SUSCEPTIBILITYSUSCEPTIBILITYGenetic/Metabolic

DNA RepairNutritional StatusNutritional Status

Immunologic StatusImmunologic Status

Tobacco and Alcohol

5.807.9

23.8

37.7

1

10

100

RelativeRisk

NSmoker 1 to 19 20 to 39 40+

Cigarettes Per Day (20+ years)

<15 to 1415 to 2930+

AlcoholDrinks/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

PittWake

Duplin

Pender

Moore

Union

Halifax

Nash

Sampson

Craven

Iredell

Johnston

Guilford

Randolph

Harnett

Brunswick

Wayne

ChathamRowan

LeeStanly

Lenoir

Franklin

Davidson

GranvillePerson

Forsyth

Caswell

Wilson

Cumberland

Orange

Gaston

Catawba

Davie

Rockingham

Alamance

Lincoln

Mecklenburg

Vance

Edgecombe

MontgomeryCabarrus

Durham

Greene

New Hanover

Onslow

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)