DESCRIPTION: (Adapted from Investigator's Abstract) It is proposed to use
the resources of three well-characterized cohort studies with prospectively
collected blood specimen banks, the Nurses Health Study, the Health
Professionals Follow-up Study, and the Physician's Health Study, to
prospectively assess gene-nutrient and other gene-environment interactions
in the etiology of colorectal cancer and adenomas. The carcinogen-
metabolizing genes the investigators will assay are N-acetyltransferase 2,
N-acetyltransferase 1, glutathione S-transferase M1 (GSTM1) and CYP1A1.
They hypothesize that "fast acetylator" NAT2 genotype, a recently described
defect in NAT1, homozygous deletions in the GSTM1 gene, and the "extensive
metabolizer" CYP1A1 genotypes are associated with increased risk of
colorectal cancer and adenomas. In addition, they will assess interactions
of known and suspected colon cancer risk factors with these genotypes,
including red meat intake, antioxidant vitamin and carotenoid intake, folate
consumption, smoking and alcohol. They expect to identify 604 cases of
colorectal cancer and 558 cases of first-adenomatous polyps; each case will
be matched by age and race to a control in a nested case-control study.
They state they will have greater than 80% power across the three studies to
prospectively assess the main effects of these genotypes with colorectal
cancer and polyps. They further state that they have substantial power to
test for interactions.
The investigators state that these studies will be among the first to
prospectively test these hypotheses, and provide population-based estimates
of attributable risks. They comment that associations with these genotypes
would implicate their substrates in cancer etiology, clarifying the specific
colon carcinogens in diet. They further comment that identifying gene-diet
interactions would suggest dietary interventions that persons with the risk
genotypes could make to reduce their risk. They conclude that confirmation
of risk genotypes would also be useful in identifying persons at high risk
of colon cancer and assist in focusing screening efforts.
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