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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040641-08
Application #
3180941
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1985-09-01
Project End
1997-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Jewel Samadder, N; Valentine, John F; Guthery, Stephen et al. (2017) Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah. Dig Dis Sci 62:2126-2132
Samadder, N Jewel; Curtin, Karen; Pappas, Lisa et al. (2016) Risk of Incident Colorectal Cancer and Death After Colonoscopy: A Population-based Study in Utah. Clin Gastroenterol Hepatol 14:279-86.e1-2
Samadder, N Jewel; Smith, Ken Robert; Hanson, Heidi et al. (2016) Familial Risk in Patients With Carcinoma of Unknown Primary. JAMA Oncol 2:340-6
Samadder, N Jewel; Jasperson, Kory; Burt, Randall W (2015) Hereditary and common familial colorectal cancer: evidence for colorectal screening. Dig Dis Sci 60:734-47
Snow, A K; Tuohy, T M F; Sargent, N R et al. (2015) APC promoter 1B deletion in seven American families with familial adenomatous polyposis. Clin Genet 88:360-5
Samadder, N J; Smith, K R; Mineau, G P et al. (2015) Familial colorectal cancer risk by subsite of primary cancer: a population-based study in Utah. Aliment Pharmacol Ther 41:573-80
Samadder, N Jewel; Smith, Ken Robert; Hanson, Heidi et al. (2015) Increased Risk of Colorectal Cancer Among Family Members of All Ages, Regardless of Age of Index Case at Diagnosis. Clin Gastroenterol Hepatol 13:2305-11.e1-2
Tuohy, Thérèse M F; Rowe, Kerry G; Mineau, Geraldine P et al. (2014) Risk of colorectal cancer and adenomas in the families of patients with adenomas: a population-based study in Utah. Cancer 120:35-42
Samadder, N Jewel; Curtin, Karen; Wong, Jathine et al. (2014) Epidemiology and familial risk of synchronous and metachronous colorectal cancer: a population-based study in Utah. Clin Gastroenterol Hepatol 12:2078-84.e1-2
Samadder, N Jewel; Curtin, Karen; Tuohy, Thérèse M F et al. (2014) Characteristics of missed or interval colorectal cancer and patient survival: a population-based study. Gastroenterology 146:950-60

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