Steroid 5-alpha-reductase type 2 (SRD5a2) is a critical enzyme in androgen metabolism. Two polymorphisms in the SRD5a2 gene, V89L (rs523349) and A49T (rs9282858), have been studied for associations with prostate cancer risk, with conflicting results. The authors conducted a systematic review and meta-analysis (1997-2007) to examine these associations and compared the results with findings from genome-wide association studies of prostate cancer. The meta-analysis included 24 case-control studies (10,088 cases and 10,120 controls for V89L and 4,998 cases and 5,451 controls for A49T). The authors found that prostate cancer was not associated with V89L (L allele vs. V allele: odds ratio = 0.99, 95% confidence interval: 0.94, 1.05) and was probably not associated with A49T (T allele vs. A allele: odds ratio = 1.10, 95% confidence interval: 0.86, 1.40). These results could have been distorted by spectrum-of-disease bias, convenience sampling of cases and controls, genotype misclassification, and/or confounding. Neither V89L nor A49T was included in microarray chips used for published genome-wide association studies. Analysis of well-designed population-based studies with pathway-based arrays containing common genetic variants could be useful for identifying genetic factors in prostate cancer.