The cyclooxygenase 2 (COX-2) enzyme overexpression in prostate cancer has led to the hypothesis that COX-2 inhibition may reduce prostate cancer growth. Some previous studies have linked the usage of COX-2 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) with a decreased prostate cancer risk. We estimated the association between cumulative COX-2 inhibition by NSAID usage and prostate cancer risk at population level. All new prostate cancer cases in Finland during 1995-2002 and matched controls (24,657 case-control pairs) were identified from national registries. Detailed information on medication purchases was obtained from a national prescription database. A total cumulative COX-2 inhibition value was calculated based on total cumulative mg amount of each NSAID drug and the drug-specific COX-1/COX-2 inhibition ratio. Prostate cancer risk was analysed with propensity score-matched conditional logistic regression model. In total, 53.8% of the cases and 46.5% of the controls had any prescription-use of NSAIDs, while 8.1% and 7.9%, respectively, had used aspirin. Compared to the non-users, any NSAID use was associated with an elevated overall prostate cancer risk (46.4% versus 53.6%, respectively; odds ratio [OR] 1.3, 95% confidence interval [CI] 1.3, 1.4) and risk of advanced cancer (11.8% versus 14.1%; OR 1.6, 95% CI 1.5, 1.8). The risk remained elevated despite the amount of cumulative COX-2 inhibition. In a separate analysis, the risk increase was similar for each NSAID with the exception of aspirin, which was associated with a decreased overall prostate cancer risk (OR 0.90, 95% CI 0.84, 0.96) in a dose-dependent fashion. NSAID use is associated with an increased prostate cancer risk at the population level regardless of the COX-2 inhibition. This may be explained by systematic differences between prescription NSAID users and non-users. In contrast, aspirin use is associated with a decreased overall prostate cancer risk. Further studies on aspirin and prostate cancer will be needed.
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