Effect of a 12-month exercise intervention on apoptosis in colon crypts: A randomized controlled trial.

A171

Alterations in proliferation and apoptosis in the highly regulated cellular growth control of the colon may play a crucial early step in the development of colorectal neoplasia. Previously, we have shown a decrease in colon crypt cell proliferation (i.e. mean height of Ki67+ nuclei) in male exercisers. Measurement of the ratio of bcl-2, an anti-apoptosis protein,to bax, an apoptosis promoting protein can yield information about apoptosis potential. Purpose: To examine the effect of a 12-month aerobic exercise intervention on bcl-2 density and bax density in colon crypts. Methods: 101 men and 98 women aged 40-75 years were randomized to a usual-lifestyle control group or a 12-month moderate-to-vigorous aerobic exercise intervention (60 min/d, 6d/wk). Colon-crypt apoptosis was measured as stained bcl-2 and bax cells in mucosal crypts obtained by flexible sigmoidoscopy at baseline and 12-months. For analysis, the stained crypt was divided into 3 regions based on deciles: bottom (interval 0.1-0.3), middle (interval 0.4-0.6) and top (interval 0.7-1.0). Results: An increase in bax density at the bottom of the crypt was seen in male exercisers compared to controls (mean change in density +1.05 vs. -0.05, p=0.05). No other changes in bcl-2 density, bax density, or bcl-2:bax ratio were seen between groups. In women, bax density at the top of the crypt was associated with amount of exercise, with changes from baseline of +0.74 (controls), -0.11 (exercisers <250 min/wk), -0.36 (exercisers 250-300 min/wk) and -0.61 (exercisers > 300 min/wk) (p=0.03), and a similar trend for improvement in aerobic fitness (VO₂max) (p=0.09) and increased number of steps/day (p=0.08). In men, bcl2:bax ratio at the bottom of the crypt was related to change in aerobic fitness (VO₂max) from baseline of +0.70 (controls), +0.12 (exercisers increased < 5% or decrease), -0.42 (exercisers increased 5-15%) and -0.48 (exercisers increased > 15%) (p=0.04). Conclusion: A12-month moderate-to-vigorous aerobic exercise intervention resulted in an increase in apoptosis at the bottom of the crypt in male exercisers compared to controls, but no change was seen in women. This is consistent with our previous findings of altered proliferation with exercise in men but not women, and with the possibility that physical activity may play a stronger role in colon cancer risk reduction in men than in women.