A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and

Background: Growing evidence shows that clinical and molecular subtypes of prostate cancer (PCa) have specific risk factors. Observational studies suggest that physical activity may lower the risk of aggressive PCa. To our knowledge, the association between physical activity and PCa defined by TMPRSS2: ERG has not been evaluated. Objective: To prospectively examine the association between physical activity and risk of PCa defined by clinical features and TMPRSS2: ERG. Design, setting, and participants: We studied 49 160 men aged 40–75 yr in the Health Professionals Follow-up Study from 1986 to 2012. Data was collected at baseline and every 2 yr with> 90% follow-up. Total and vigorous physical activity were measured in metabolic equivalent of task (MET)-h/wk.Outcome measures and statistical analysis: Advanced PCa was defined as stage T3b, T4, N1, or M1 at diagnosis and lethal PCa as distant metastases or death due to disease over follow-up. Presence of TMPRSS2: ERG was estimated by immunohistochemistry of ERG protein expression. Cox proportional hazards models were used to obtain multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of subtype-specific PCa. Results and limitations: During 26 yr of follow-up, 6411 developed PCa overall and 888 developed lethal disease. There were no significant associations between total physical activity and risk of PCa in the overall cohort. In multivariable-adjusted models, men in the highest quintile of vigorous activity had a significant 30% lower risk of