Recent work by us and others indicates that both environmental factors, primarily diet, and inherited susceptibility are important in the pathogenesis of colonic adenomatous polyps and colorectal cancer. How environmental risk factors affect the expression of inherited susceptibility is not known. We now have the opportunity to examine this question by evaluating diet and other environmental factors in a Utah kindred of over 4000 members in which an inherited susceptibility for colonic adenomatous polyps and colon cancer segregates. The gene responsible for colonic neoplasms in this kindred maps to the adenomatous polyposis coli (APC) locus, although the phenotype in the kindred is very different from that of APC. The phenotype is characterized by a variable number of adenomatous polyps and a high risk for colon cancer. To perform the study we will first identify gene carriers in the kindred using heplotype genetic markers. We will then examine gene carriers by colonoscopy to determine adenomatous polyp expression, and assess environmental variables in these same individuals. The effect of environmental factors on adenoma expression in gene carriers will be determined by comparing gene carriers who exhibit many adenomatous polyps with gene carriers who exhibit few or no adenomatous polyps for differences in environmental exposure. The effect of environmental exposures on other adenomatous polyp characteristics such as size, degree of dysplasia and colonic location will also be examined. The environmental variables to be tested against polyp expression include dietary fat, protein, fiber, total calories, calcium, vitamin D, beta carotene and other carotenoids; consumption of fruits, vegetables and dairy products; serum cholesterol (LDL, HDL and total), triglycerides, beta carotene, and calcium; physical activity and body size; and alcohol and tobacco use. The investigation is significant because it provides the first opportunity to study the effects of environmental risk factors on the development of adenomatous polyps in the setting where individual genetic susceptibility is known.
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