Statin use and risk of prostate cancer: a meta-analysis of observational studies

Abstract

Background: Emerging 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.

Methods: Literature 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.

Results: A 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.

Conclusions: Our 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.

Figure 1. Flowchart representing the selection process.

Figure 2. Assessment of publication bias.

Funnel plot (publication bias assessment plot) of the relative risk of developing prostate cancer, by the standard error, for all studies. Circles- studies included in the meta-analysis. Relative risks are displayed on a logarithmic scale. p = 0.56 for the Begg's test, and p = 0.12 for the Egger's test.

Figure 3. Statin use and risk of prostate cancer.

Pooled estimate of relative risk (RR) and 95% confidence intervals (CIs) of total prostate cancer (PCa) associated with statin use based on 27 [in figure study by Sato et al. is excluded due to its large CI (RR 4.56, 95% CI 0.06–25.39) and no effect on the final pooled estimated RR] studies (15 cohort and 12 case-control studies) involving more than 1.8 million participants including 56,847 PCa cases. Squares indicate RR in each study. The square size is proportional to the weight of the corresponding study in the meta-analysis; the length of horizontal lines represents the 95% CI. The unshaded diamond indicates the pooled RR and 95% CI (random-effects model).

Figure 4. Long-term statin use and risk of prostate cancer.

Pooled estimate of relative risk (RR) and 95% confidence intervals (CIs) of total prostate cancer (PCa) associated with long-term statin use based on 11 studies (7 cohort and 4 case-control studies) involving 273,798 participants including 3,702 PCa cases. Squares indicate RR in each study. The square size is proportional to the weight of the corresponding study in the meta-analysis; the length of horizontal lines represents the 95% CI. The unshaded diamond indicates the pooled RR and 95% CI (random-effects model).

Figure 5. Statin use and risk of advanced prostate cancer.

Pooled estimate of relative risk (RR) and 95% confidence intervals (CIs) of advanced prostate cancer (PCa) associated with statin use based on 7 studies (5 cohort and 2 case-control studies) involving 266,209 participants including 5,236 advanced PCa cases. Squares indicate RR in each study. The square size is proportional to the weight of the corresponding study in the meta-analysis; the length of horizontal lines represents the 95% CI. The unshaded diamond indicates the pooled RR and 95% CI (fixed-effects model).