Effect of a 12-Month Exercise Intervention on Patterns of Cellular Proliferation in Colonic Crypts: A Randomized Controlled Trial

Abstract

Colon crypt architecture and proliferation may be appropriate biomarkers for testing prevention interventions. A hypothesized mechanism for exercise-induced colon cancer risk reduction might be through alterations in colon crypt cell architecture and proliferation. Healthy, sedentary participants with a colonoscopy within the previous 3 years were recruited through gastroenterology practices and media. We randomly assigned 100 women and 102 men, ages 40 to 75 years, to a control group or a 12-month exercise intervention of moderate-to-vigorous aerobic exercise, 60 minutes per day, 6 days per week, and assessed change in number and relative position of Ki67-stained cells in colon mucosal crypts. Exercisers did a mean 370 min/wk (men) and 295 min/wk (women) of exercise (seven dropped the intervention). In men, the mean height of Ki67-positive nuclei relative to total crypt height was related to amount of exercise, with changes from baseline of 0.0% (controls), +0.3% (exercisers <250 min/wk), -1.7% (exercisers 250-300 min/wk), and -2.4% (exercisers >300 min/wk; P(trend) = 0.03). In male exercisers whose cardiopulmonary fitness (V(O(2))max) increased >5%, the mean height of Ki67-positive nuclei decreased by 2% versus 0.9% in other exercisers, and versus no change in controls (P(trend) = 0.05). Similar trends were observed in other proliferation markers. In women, increased amount of exercise or V(O(2))max did not result in notable changes in proliferation markers. A 12-month moderate-to-vigorous intensity aerobic exercise intervention resulted in significant decreases in colon crypt cell proliferation indices in men who exercised a mean of >/=250 min/wk or whose V(O(2))max increased by >/=5%.