The investigators are jointly undertaking two NCI-funded case-control studies of colon cancer (2400 cases and 2400 controls)(R01 CA48998) and adenomatous polyps of the large bowel (600 cases and 1800 controls)(P01 CA50305), investigating the role of diet, physical activity, reproduction, and family history. The two studies were designed to answer similar questions using similar instruments. Blood is being collected in both study populations and a storage system for future access to white cell and DNA on well characterized colon neoplasia patients has been established (R01 CA 56631). It is increasingly clear that, in addition to the environmental factors, genetic susceptibility is important in the etiology of these disorders. Since the original submission of CA48998, much progress has been made in Utah and elsewhere in identifying genes associated with colon cancer. The FAP gene - APC - is located at 5q21 and has been sequenced, allowing genotyping of the case-control study subjects. Further, acetylator genotype, for which there is evidence of an association both with colon cancer and with the metabolism of known dietary carcinogens, can now be established using a PCR-based allele-specific amplification technique.
The specific aims of this proposal are: 1. To analyze DNA from all participants to explore the role of acetylator status and the APC gene in the etiology of colon neoplasia; 2. To explore the evidence for confounding and interaction between the genotypes and diet, particularly intake of meat, fat, protein, but also of total calories, calcium, micronutrients, and fiber, and physical activity, reproduction, and family history, in the etiology of colon neoplasia; The combined environment/diet/gene dataset will provide the first, the most cost-effective, and perhaps the most comprehensive opportunity to determine the way in which genes and environment interact in the etiology of colon cancer and its precursor lesion.
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