This research examines the effect of different levels of dietary fat and fiber on the proliferation and death of colonic epithelial cells. Subjects are given a well-controlled diet (weight maintaining, metabolic), with fat/fiber combination (high, normal or low fat and high, normal or low fiber) as the independent variable. Upon admission, after baseline endoscopic biopsy (by flexible sigmoidoscopy), subjects are placed on a low fat, high fiber diet for 4 wks. Assessment of colonic epithelium, sodium butyrate, and Ki-ras oncogene mutations are performed using endoscopic biopsy, blood, and stool sample. SIGNIFICANCE OF STUDY: Colon cancer is a common human malignancy. Dietary fat and fiber have been shown to affect the incidence of colorectal cancer. Populations consuming diets high in fat and low in fiber overall have greater incidence rates of colorectal cancer, compared to populations consuming less fat and more fiber. It is not entirely clear whether dietary fat and fiber are independent variables with respect to colon carcinogenesis. Sodium butyrate, a short chain fatty acid, is generated in the colon in large quantities as dietary fiber is fermented by colonic bacteria. Sodium butyrate, in vitro, reduces the proliferation and induces apoptosis in cultured colon cancer cells. FUTURE PLANS: Once a sufficient subject population is studied and laboratory and statistical analyses are completed, we will be able to determine the effects of dietary fat and fiber on several parameters in the colonic mucosa which might be important indicators of colon cancer risk. Additional studies will focus on the level of fat and fiber that produces the highest risk for colon cancer and eventually to isolate those substances in this diet that are responsible for predisposition to colon cancer.
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