AB Purpose: This study aimed to test prospectively whether exercise is associated with lower brain cancer mortality in 111,266 runners and 42,136 walkers from the National Runners' and Walkers' Health Studies. Methods: Hazard ratios and 95% confidence intervals (95% CI) from Cox proportional hazards analyses of mortality versus metabolic equivalent hours per day of exercise (MET-hours per day, where 1 MET = 3.5 mL O2[middle dot]kg-1[middle dot]min-1, or approximately 1-km run). Results: The National Death Index identified 110 brain cancer deaths during an 11.7-yr average follow-up. Runners and walkers were combined because the brain cancer risk reduction did not differ significantly between MET-hours per day run and MET-hours per day walked (P = 0.66). When adjusted for sex, age, race, education, and cohort effects, the risk for brain cancer mortality was 43.2% lower for those who exercised 1.8 to 3.5 MET[middle dot]h[middle dot]d-1 (95% CI = 2.6%-66.8% lower, P = 0.04) and 39.8% lower for those who exercised >=3.6 MET[middle dot]h[middle dot]d-1 (95% CI = 0.0%-64.0% lower, P = 0.05) compared with <1.8 MET[middle dot]h[middle dot]d-1 at baseline. Pooling the runners and walkers who expended >=1.8 MET[middle dot]h[middle dot]d-1 showed a 42.5% lower risk of brain cancer mortality for the entire sample (95% CI: 8.0 to 64.1, P = 0.02) and 40.0% lower risk when three deaths that occurred within 1 yr of the baseline survey were excluded (95% CI = 1.3%-62.4%, P = 0.04). Conclusions: The risk for fatal brain cancer decreased in association with running and walking energy expenditure. Our ability to detect an exercise-brain cancer relationship may relate to the use of cohorts specifically designed to detect exercise-health associations, and the calculation of exercise energy expenditure from kilometers per day walked and run rather than time spent exercising.
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