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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