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

¹ Cancer Prevention Program, Fred Hutchinson Cancer Research Center; ² Departments of Epidemiology, ³ Medicine, and ⁴ Pathobiology, University of Washington; ⁵ Health Services Research and Development Program, Veterans Affairs Puget Sound Health Care System; ⁶ Virginia Mason Medical Center, Seattle, Washington; ⁷ Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut; and ⁸ Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada

Requests for reprints: Anne McTiernan, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024. Phone: 206-667-7979; Fax: 206-667-7850. E-mail: amctiern{at}fhcrc.org

Background: 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.

Methods: 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.

Results: 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_O2max) 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_O2max did not result in notable changes in proliferation markers.

Conclusions: 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_O2max increased by 5%. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1588–97)

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