Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Highway, MS K55, Atlanta, GA 30341, USA.
Am J Epidemiol. 2010 Jan 1;171(1):1-13. doi: 10.1093/aje/kwp318. Epub 2009 Nov 13.
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.
5α-还原酶 2 型（SRD5a2）是雄激素代谢中的关键酶。SRD5a2 基因中的两个多态性，V89L（rs523349）和 A49T（rs9282858），已被研究与前列腺癌风险相关联，但结果存在冲突。作者进行了系统评价和荟萃分析（1997-2007 年），以检查这些关联，并将结果与前列腺癌全基因组关联研究的结果进行比较。荟萃分析包括 24 项病例对照研究（V89L 为 10088 例病例和 10120 例对照，A49T 为 4998 例病例和 5451 例对照）。作者发现前列腺癌与 V89L 无关（L 等位基因与 V 等位基因：比值比=0.99，95%置信区间：0.94，1.05），并且可能与 A49T 无关（T 等位基因与 A 等位基因：比值比=1.10，95%置信区间：0.86，1.40）。这些结果可能因疾病谱偏倚、病例和对照的方便抽样、基因型分类错误和/或混杂因素而失真。V89L 和 A49T 均未包含在用于已发表的全基因组关联研究的微阵列芯片中。对基于人群的设计良好的研究进行基于途径的分析，其中包含常见的遗传变异，可能有助于确定前列腺癌中的遗传因素。
