Colorectal cancer remains the second leading cause of cancer death in the United States with an estimated 53,000 deaths and 152,000 new cases diagnosed in 1993. Recent advances in effective adjuvant chemotherapy are just beginning to impact 5-year survival rates. As a result, early diagnosis and especially dietary and novel chemopreventive strategies represent the best hope for significantly decreasing the high mortality rates from this disease. Sporadic adenomatous colorectal polyps are a recognized precursor of the large majority of colorectal cancers and preventive efforts have focused on their early detection and removal by colonoscopy. We have crafted a Colon Cancer Program Project that has a unifying hypothesis - low fecal and plasma bile acid concentrations (related to high fiber and/or low fat dietary intakes) are associated with reduced progression of DNA damage in neoplastic colorectal epithelial cells (assessed by the prevalence of K-ras, DCC and p53 genetic alterations as well as DNA ploidy status in index and/or recurrent adenomas), diminished cellular proliferation in non-neoplastic colorectal epithelium (assessed by reduced protein kinase C isozyme activity and/or expression and low rates of proliferating cell nuclear antigen labeling) and significant reductions in colorectal adenoma recurrence rates. We have assembled a large team of highly interactive basic and clinical scientists from four universities to successfully complete three scientific projects: Project I: Phase III study of the effect of wheat bran fiber on adenomatous polyp recurrence and bile acid concentrations in blood and feces, and rectal mucosal proliferation rates in patients with adenomatous colorectal polyps. Project II: Phase III study of the effects of ursodeoxycholic acid on adenomatous polyp recurrence, bile acid concentration in blood and feces, and rectal mucosal proliferation rates in patients with adenomatous colorectal polyps. Project III: A study of genetic alterations in adenomatous polyps associated with dietary fat and fiber and bile acids. The three cores, Administration, Biometry and Services (Analytical, Nutrition, Adherence) provide the structure and expertise for successful execution of the clinical- and laboratory-based Projects. A specialized quality assurance/quality control program further monitors each of the 3 research projects.
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