Dosage, duration and timing of nonsteroidal antiinflammatory drug use and risk of prostate cancer

Abstract

Experimental studies suggest that NSAIDs could reduce prostate cancer risk. Results of observational studies on the relation between NSAIDs and prostate cancer risk have, however, been inconsistent. Moreover, none has addressed the issues of dosage, duration and timing of exposure. In a population-based, age-matched case-control study, we measured the association between prostate cancer risk and NSAIDs defined in terms of mean daily dose, cumulative duration and timing of exposure. Eight-year drug exposure history was obtained from the Quebec health insurance system database. Parallel analyses were performed for aspirin and NSAIDs other than aspirin. We controlled for detection bias and assessed the potential impact of protopathic bias. Analyses were performed with conditional logistic regression. Among the 2,221 cases and 11,105 controls, there was a negative trend between cumulative duration of aspirin use and prostate cancer risk (p ‫؍‬ 0.0009). Also, exposure to a mean daily dose of aspirin of at least 80 mg, maintained throughout the entire 8 years of follow-up, was associated with an 18% reduction in prostate cancer risk (OR ‫؍‬ 0.82, 95% CI 0.71-0.95). In more recent users of such a dose, the risk reduction was 7%. However, 1 year after the end of a 7-year regular aspirin exposure, no residual protective effect persisted. No association was observed between prostate cancer risk and exposure to NSAIDs other than aspirin. The results suggest that long-term and regular use of aspirin, at a dosage beneath that usually recommended for an anti-inflammatory effect, may prevent prostate cancer.

Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis

“…We identified 12 reports (10 manuscripts and two unpublished reports) that met the inclusion criteria (Paganini-Hill et al, 1989;Schreinemachers and Everson, 1994;Neugut et al, 1998;Norrish et al, 1998;Langman et al, 2000;Nelson and Harris, 2000;Habel et al, 2002;Irani et al, 2002;Leitzmann et al, 2002;Menezes et al, 2002;Roberts et al, 2002;Perron et al, 2003). Two other studies were excluded because they evaluated outcomes other than incident prostate cancer: a case -control study that measured the prevalence of prostate cancer in autopsies of analgesics abusers (OR ¼ 0.84; 95% confidence interval (CI): 0.36 -1.98) (Bucher et al, 1999) and a cohort study that measured mortality from male genital cancers (rate ratio ¼ 0.82; 95% CI: 0.56 -1.19) (Thun et al, 1993).…”

“…For studies that measured exposure to NA-NSAIDs, the summary OR was 0.87 (95% CI: 0.61 -1.24) with substantial heterogeneity between studies (P ¼ 0.005). Heterogeneity was primarily caused by the inclusion of a large Canadian prospective study (Perron et al, 2003) that reported an OR of 1.2 (95% CI: 1.02 -1.4) for NA-NSAID use. Excluding this study, the summary OR is 0.73 (95% CI: 0.49 -1.1) and heterogeneity is greatly reduced (P ¼ 0.151).…”

“…(Paganini-Hill et al, 1989;Norrish et al, 1998;Langman et al, 2000). The study that was best equipped to address this issue (Perron et al, 2003), in terms of power and availability of detailed exposure data, reported a stronger inverse association with larger doses of aspirin, but only among participants who used aspirin for X4 years. This study also found a negative trend of prostate cancer risk with duration of use; the ORs decreased from about 1 for p4 years of use to 0.66 for men who used aspirin for X6 years.…”

“…over the counter use) and were based on the assumption that the amount of NSAIDs dispensed is a good approximation of actual consumption. This may not be true especially for NSAIDs other than aspirin that are frequently prescribed to be taken only when needed (Perron et al, 2003). More importantly, in most studies exposure was simply categorised as 'ever use' or 'frequent use' vs 'never use'.…”

Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer

“…In addition, several studies have already recognized that nonsteroidal anti-inflammatory drugs have a dramatic antitumor effect in prostate cancer both in vivo (45) and in vitro (10). Additionally, a cohort study (46) and a case-control study (47) report strong inverse associations between nonsteroidal antiinflammatory drug intake and risk of prostate cancer. with various Gleason scores.…”