Colorectal cancer is the second most common internal malignancy and second leading cause of cancer related deaths in the U.S. today. New methods of determining risk for colorectal cancer development are urgently needed so that chemopreventive strategies can be effectively applied. Epidemiologic evidence strongly suggests that the high-fat """"""""Western type"""""""" diet may contribute to colorectal cancer risk by causing the colon to be exposed to byproducts of dietary fat metabolism which may initiate or promote cancer. Up to 40% of people eating a """"""""Western type"""""""" diet excrete species in feces which are active in mutagenic assays. Recently, the compounds responsible for the majority of mutagenic activity in stool have been identified. These compounds called fecapentenes, are highly unsaturated enol-ether derivatives of dietary fat. No data are available as yet which address the relationship of fecapentene excretion in the stool to dietary fat intake. This study proposes to begin to address the relationship of fecapentene excretion dietary intake and colorectal cancer risk by quantitatively comparing fecapentene excretion in a population of patients with a well defined increased risk of colorectal cancer i.e., a group of ulcerative colitis patients, to that of an age-matched group of """"""""normal risk"""""""" control volunteers. Stool samples will be collected during Clinical Research Center admission under defined and standardized dietary intake. Fecapentene excretion will be quantitated by high performance liquid chromatographic analysis of partially purified extracts of 3 separate stool samples provided by each patient and volunteer. In addition, control subjects will be instructed in a low-fat diet designed to reduce the percentage of calories from fat to 20% for a period of 30 days, following which quantitative fecapentene excretion in the stool will be redetermined during a second Clinical Research Center admission while on a 20% fat diet. This phase will address the question of whether a dietary intervention is associated with fecapentene excretion.
