Head and Neck Cancer Study CHANCE

1
Head and Neck Cancer StudyCHANCE

• Oral, pharynx, larynx cancer
• Priority--Gene-exposure interactions
• Tobacco, alcohol
• Phase I, Phase II, DNA repair gene polymorphisms
  (22 cSNPs)
• NC study, 46 counties
• 3,100 individuals (1,500 cases, 1,600 controls)
• In-person interview, blood or buccal, tumor
  blocks
• Interview 297 major items, 1,017 total items
  (Stored in SAS)
• Standard case-control, haplotypes
• Access ( Oracle) systems for subject and
  specimen tracking
• SAS/STATA and other software for analysis

2
Centers for Birth Defects
Research Prevention
3
National Birth Defects Prevention Study

• Case-control study of major birth defects
• 10 US Centers
• Enrollment began with births on or after 10/1/97
  
• NC funded 9/02. A. Olshan, PI

4
Study Purpose

• Evaluate genetic and environmental factors
  associated with birth defects
• Test hypotheses regarding etiology
• - Suspected teratogens
• - Gene-environment interactions
• - Gene-gene interactions

5
Study Population

• Case infants
• Identified from birth defects surveillance
  registries
• Liveborn, stillborn, or induced abortion
• Control infants
• Identified from vital records or birth hospitals
• No major birth defects
• Goal for each center 300 cases and 100 controls
  per year

6
Defects Included in NBDPS

• Neural tube defects
• Holoprosencephaly
• Hydrocephalus
• Dandy-Walker malformation
• An/microphthalmia
• Cataracts/glaucoma
• Anotia, microtia
• Heart defects
• Choanal atresia
• Cleft lip
• Cleft palate
• Esophageal atresia/TE fistula

• Intestinal atresia/stenosis
• Biliary atresia
• Hypospadias, second/third degree
• Renal agenesis/hypoplasia
• Exstrophy, bladder/cloacal
• Limb deficiency
• Craniosynostosis
• Diaphragmatic hernia
• Sacral agenesis
• Omphalocele
• Gastroschisis
• Amnion rupture sequence

7
National Birth Defects Prevention Study

• Clinical database entry/review
• Maternal interview
• Buccal cell (DNA) collection

8
NBDPS Computer Assisted Telephone Interview

• Maternal Interview
• Structured questionnaire in English or Spanish
• Standardized database
• Questions about pregnancy and medical histories,
  diet, lifestyle, occupational and environmental
  exposures, and medication use
• Incentives

9
NBDPS Biologics (DNA) Collection

• Kit mailed to family includes brush for cheek
  cell collection
• Cheek cells collected from infant, mother, father
• DNA extracted quality control performed at
  each Center
• Portion of DNA banked at CASPIR
• Biologics database linked to clinical and
  interview data

10
How much data?

• 13,558 Cases 5019 Controls
• Interview dataset
• 118 major (exposure) questionnaire items
• 4,747 total data items in questionnaire
• CDC building genotype database
• About 100 cSNPs, plans for genome scan

11
Informatics

• CDC developed Access system for clinical review,
  subject and specimen tracking system
• Interview database in Access converted to SAS
• Format for centralized genotype database
  undecided
• Major analyses in SAS and specialized software

12
NC Research Proposal

• DNA Repair Gene Polymorphisms
• Neural tube defects, oral clefts, selected heart
  defects
• 11 cSNPs for 6 BER, NER, DSB repair genes
• htSNPs using EGP
• 1,500 repair gene snp chip?
• Case-control analyses- gene, gene X gene, G x E
• Logistic regression, Hierarchical regression
• Case-only, Trios