Effect of Exercise on Biomarkers of Colon Cancer Risk

There is strong observational epidemiologic evidence that physical activity is inversely associated with risk of colon cancer occurrence in both men and women. This association has been found in over 30 observational studies, and appears to be independent of effects of diet, body fat mass, and other potential confounding factors. Prior to large-scale recommendations regarding exercise as a means of preventing colon cancer, however, more information is needed regarding the type of exercise, when it must be initiated, and how much must be done, in order to produce a protective effect. Information on the mechanisms and biological pathways through which exercise might protect the colon will aid in developing the answers to these questions. This is a randomized controlled trial of a one-year moderate/vigorous exercise intervention vs. delayed- exercise control on various biomarkers of colon cancer risk in persons that have undergone a colonoscopy within the past 36 months.. The trial is designed to establish the effects of the exercise intervention on colorectal cell proliferation and terminal differentiation, and on factors that may lie in the pathway between exercise and proliferation and apoptosis, in colon and rectal epithelium. It will provide data on: 1) the efficacy of a one-year moderate intensity aerobic exercise program in modulating these processes to a pattern considered low risk for colon cancer, and 2) the mechanisms whereby exercise may lower colon cancer risk in humans. To the investigators' knowledge, this will be the first study of its kind.

The specific aims of the proposed study are: 1. To measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. a delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on proliferation rate in the upper part of colon and rectal mucosa crypts. 2. To also measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on: * expression of apoptosis-related proteins (bax/bcl-2 ratio) in colon and rectal mucosal biopsies * rectal mucosal prostaglandin levels * fasting serum/plasma insulin, glucose, triglycerides, insulin-like growth factor 1(IGF-1), and IGF binding protein-3 (IGFPB-3) * body fat mass and distribution (body mass index, waist and hip circumferences, bioelectrical impedance, DEXA scan) * subcutaneous abdominal and intra-abdominal fat mass (measured by one-slice CT scan at the L4 level) * fitness (VO2max) * quality of life (measured by standardized self-report instruments) * sleep quality