Associations of aspirin, nonsteroidal anti-inflammatory drug and paracetamol use with PSA-detected prostate cancer: findings from a large, population-based, case-control study (the ProtecT study)

Evidence from laboratory studies suggests that chronic inflammation plays an important role in prostate cancer aetiology. This has resulted in speculation that nonsteroidal anti-inflammatory drugs may protect against prostate cancer development. We analysed data from a cross-sectional case-control study (n(cases) = 1,016; n(controls) = 5,043), nested within a UK-wide population-based study that used prostate specific antigen (PSA) testing for identification of asymptomatic prostate cancers, to investigate the relationship of aspirin, nonsteroidal anti-inflammatory drug (NSAID) and paracetamol use with prostate cancer. In conditional logistic regression models accounting for stratum matching on age (5-year age bands) and recruitment centre, use of non-aspirin NSAIDs [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.04-1.67] or all NSAIDs (OR = 1.25; 95% CI = 1.07-1.47) were positively associated with prostate cancer. There were weaker, not conventionally statistically significant, positive associations of aspirin (OR = 1.13; 95% CI = 0.94-1.36) and paracetamol (OR = 1.20; 95% CI = 0.90-1.60) with prostate cancer. Mutual adjustment for aspirin, non-aspirin NSAIDs or paracetamol made little difference to these results. There was no evidence of confounding by age, family history of prostate cancer, body mass index or self-reported diabetes. Aspirin, NSAID and paracetamol use were associated with reduced serum PSA concentrations amongst controls. Our findings do not support the hypothesis that NSAIDs reduce the risk of PSA-detected prostate cancer. Our conclusions are unlikely to be influenced by PSA detection bias because the inverse associations of aspirin, NSAID and paracetamol use with serum PSA would have attenuated (not generated) the observed positive associations.