Abstract
BackgroundEmerging evidence suggests that statins may decrease the risk of cancers. However, available evidence on prostate cancer (PCa) is conflicting. We therefore examined the association between statin use and risk of PCa by conducting a detailed meta-analysis of all observational studies published regarding this subject.MethodsLiterature search in PubMed database was undertaken through February 2012 looking for observational studies evaluating the association between statin use and risk of PCa. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed.ResultsA total of 27 (15 cohort and 12 case-control) studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Statin use significantly reduced the risk of both total PCa by 7% (RR 0.93, 95% CI 0.87–0.99, p = 0.03) and clinically important advanced PCa by 20% (RR 0.80, 95% CI 0.70–0.90, p<0.001). Long-term statin use did not significantly affect the risk of total PCa (RR 0.94, 95% CI 0.84–1.05, p = 0.31). Stratification by study design did not substantially influence the RR. Furthermore, sensitivity analysis confirmed the stability of results. Cumulative meta-analysis showed a change in trend of reporting risk from positive to negative in statin users between 1993 and 2011.ConclusionsOur meta-analysis provides evidence supporting the hypothesis that statins reduce the risk of both total PCa and clinically important advanced PCa. Further research is needed to confirm these findings and to identify the underlying biological mechanisms.
Highlights
Prostate cancer (PCa) is the sixth leading cause of cancer death in males worldwide [1]
Five studies reported a negative association between statin use and risk of total prostate cancer (PCa) [5,6,25,26,28]
We found a significant inverse association between statin use and risk of total PCa among cohort studies (RR 0.93, 95% confidence intervals (CIs) 0.87–1.01, p = 0.09) but non-significant inverse association among case-control studies (RR 0.87, 95% CI 0.72–1.05, p = 0.15)
Summary
Prostate cancer (PCa) is the sixth leading cause of cancer death in males worldwide [1]. The developed countries carry most of the disease burden, accounting for nearly three quarters (72%) of the total in 2008 [2]. It is the second leading cause of cancer death in American men, after lung cancer [3]. Some randomized clinical trials (RCTs) on statin use in coronary heart disease [18,19], report nonsignificant decreased incidence of PCa among statin users compared to non users, but most of the results were ambiguous because of inadequate power. There is only one on-going clinical trial (simvastatin vs placebo) which examines the biologic effects of statins on prostate cancer in humans [20]. We examined the association between statin use and risk of PCa by conducting a detailed meta-analysis of all observational studies published regarding this subject
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