Long‐term aspirin use and the risk of total, high‐grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988–2006

<jats:title>Abstract</jats:title><jats:p>Experimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40–75 years at baseline, we evaluated long‐term aspirin use and the incidence of total, high‐grade (Gleason 8‐10, <jats:italic>n</jats:italic> = 488), regionally advanced (T3b‐T4 or N1, <jats:italic>n</jats:italic> = 228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, <jats:italic>n</jats:italic> = 580) from 1988–2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18‐year study period. Men taking ≥ 2 adult‐strength aspirin tablets a week had a 10% lower risk of prostate cancer (<jats:italic>p</jats:italic>‐for‐trend = 0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high‐grade and lethal disease, men taking ≥ 6 adult‐strength tablets/week experienced similar reductions in risk hazard ratio [HR = 0.72 (95% confidence intervals [CI]: 0.54, 0.96) and HR = 0.71 (95% CI: 0.50, 1.00)]. Analytical approaches to address bias from more frequent prostate‐specific antigen screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high‐grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer.</jats:p>