Strong observational evidence points to a link between physical activity and reduction in risk of colon cancer. The mechanisms for this association have not been delineated, nor have the amounts and types of exercise needed for a putative protective effect been determined. We propose a randomized controlled clinical trial of a one-year moderate aerobic/strength training exercise intervention in adenomatous colon polyp patients (n=100 men, 100 women). We hypothesize that polyp patients in an exercise intervention will experience significant biological effects on colorectal epithelium, specifically Ki67 indices of proliferation, bax and bc1-2 markers of apoptosis, and prostaglandin concentrations (PGE2 and PGF2cc). Patients will be recruited on-site from gastroenterology physicians' offices and secondarily from a high-risk colorectal cancer family registry. Sedentary individuals with newly diagnosed (within the past 18 months) adenomatous colon polyp(s) will be screened for eligibility and randomized to either the exercise intervention or a stretching-control group. The exercise intervention will use existing proven methods for adopting and maintaining exercise, taken from our ongoing research program. It will consist of 3 months' facility-based exercise instruction in small groups, followed by 9 months' home-based exercise program supplemented with group behavior change meetings. The goal for exercise will be moderate-level aerobic exercise 5-6 days per week for 30-45 minutes, plus strength training 2 days per week for 15-20 minutes. Colon and rectal biopsies will be taken at baseline and 12-months, and examined for amount and patterns of epithelial cell proliferation (with Ki67 marker) and apoptosis markers (bc1-2 and bax, an inhibitor and an inducer of apoptosis, respectively). Additional potential markers of exercise effect on colon cancer risk will be measured, including rectal mucosal biopsy prostaglandin concentrations, stool frequency, insulin-like growth factor (IGF-1) and IGF binding protein (IGFBP-3), insulin, glucose, C-peptide, triglycerides, and measures of fat mass and fat distribution. Other measures at baseline and 12 months include fitness (V02max), self-reported physical activity, diet, and quality of life. Results from this unique human experimental study will provide important information about mechanisms of exercise effects on colon carcinogenesis and about potential
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