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
• Environmental
• Lifestyle
5%
45%
• Occupational
• Pharmacologic • Biologic (viruses)
4%
2% 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
Head and Neck Cancer as a Model for Gene-Environment Interaction
Andrew F. Olshan, Ph.D. Departments of Epidemiology and Otolaryngology/Head & Neck Surgery University of North Carolina
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 Preneoplastic lesions Recurrence/second primaries
• Other Characteristics
– –
Exposure
Biologically Effective Dose
Internal Dose DNA Adducts Agent or Metabolites
Preclinical Biologic Effect
Mutation
Oncogenes Tumor Suppressor
SUSCEPTIBILITY
Genetic/Metabolic DNA Repair
Nutritional Status Immunologic Status
Preneoplastic Lesions
CLINICAL DISEASE
Tobacco and Alcohol
Alcohol
Drinks/Wk
100
<1 5 to 14 15 to 29 30+
37.7 23.8
Relative Risk 10
7.9 5.80
1 NSmoker
From Blot 88
1 to 19
20 to 39
40+
Cigarettes Per Day (20+ years)
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
Halifax Forsyth Guilford Alamance Franklin Orange Nash Davie Durham Edgecombe Davidson Iredell Randolph Chatham Wilson Wake Catawba Rowan Pitt Johnston Lincoln Greene Lee Cabarrus Montgomery Harnett Stanly Gaston Moore Wayne Lenoir Craven Mecklenburg Cumberland Union Sampson Duplin Onslow Pender Vance Rockingham Person Caswell Granville
Brunswick
New Hanover
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 – ADH2
– AGT – XPD
NQO1 ADH3
XRCC1
MPO ADH4
APE1
MnSOD
HOGG1
CHANCE Study
• Tumor Blocks • Tumor expression arrays • Medical Records
• • • •
Social Factors Access to Health Care Screening Follow-up of Cases (new survivor study)