Download Cancer Epidemiology An Introduction

Cancer Epidemiology
An Introduction
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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
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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
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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
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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 Epidemiology
Current/Future Topics
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Infectious Agents
Obesity
Physical Activity
Diet
Hormones
Immunologic Factors
Inherited Susceptibility (Polymorphisms)
Cancer Epidemiology
Current/Future Topics
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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
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Tumor Suppressor Genes
Oncogenes
Virus
• Other Characteristics
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Preneoplastic lesions
Recurrence/second primaries
Exposure
Biologically
Effective Dose
Internal Dose
DNA Adducts
Agent
or
Metabolites
SUSCEPTIBILITY
Preclinical
Biologic
Effect
Mutation
Oncogenes
Tumor Suppressor
Preneoplastic
Lesions
Genetic/Metabolic
DNA Repair
Nutritional Status
Immunologic Status
CLINICAL
DISEASE
Tobacco and Alcohol
100
Alcohol
Drinks/Wk
37.7
<1
5 to 14
15 to 29
30+
Relative
Risk 10
23.8
7.9
5.80
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NSmoker
From Blot 88
1 to 19
20 to 39
Cigarettes Per Day (20+ years)
40+
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
Vance
Rockingham
Person
Caswell
Granville
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
Brunswick
New Hanover
CHANCE STUDY
– DMV Controls
– Phone number search, letter, phone call
– Frequency Matched (age, race, gender)
CHANCE STUDY
– In-person interview
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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
NQO1
ADH3
– AGT
– XPD
XRCC1 APE1
MPO
ADH4
MnSOD
HOGG1
CHANCE Study
• Tumor Blocks
• Tumor expression arrays
• Medical Records
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Social Factors
Access to Health Care
Screening
Follow-up of Cases (new survivor study)