cancer epidemiology an introduction the epidemiologic perspective aims of cancer epidemiology...
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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)