Effect of a 12-month exercise intervention on patterns of cellular proliferation in colonic crypts: a randomized controlled trial.
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(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.


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(O(2))max increased by >/=5%.
McTiernan
Anne
A
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024, USA. amctiern@fhcrc.org
Yasui
Yutaka
Y
Sorensen
Bess
B
Irwin
Melinda L
ML
Morgan
Angela
A
Rudolph
Rebecca E
RE
Surawicz
Christina
C
Lampe
Johanna W
JW
Ayub
Kamran
K
Potter
John D
JD
Lampe
Paul D
PD
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology*; D015444:Exercise; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption
D019394:Ki-67 Antigen