Pearce C Leigh, Van Den Berg David J, Makridakis Nick, Reichardt Juergen K V, Ross Ronald K, Pike Malcolm C, Kolonel Laurence N, Henderson Brian E
1Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Hum Mol Genet. 2008 Aug 15;17(16):2456-61. doi: 10.1093/hmg/ddn145. Epub 2008 May 10.
The steroid 5-alpha reductase type II gene (SRD5A2) encodes the enzyme which converts testosterone (T) to the more active androgen dihydrotestosterone. A non-synonymous single-nucleotide polymorphism, A49T (rs9282858), in SRD5A2 has been implicated in prostate cancer risk; however, results have been inconsistent. In 1999, we reported a strong association between the A49T variant and prostate cancer risk among African-Americans and Latinos in the Hawaii-Los Angeles Multiethnic Cohort (MEC). We report here an updated analysis of MEC data including the five major ethnic groups of the MEC, an increased sample size, improved genotyping technology and a comprehensive meta-analysis of the published literature. We found a non-statistically significant positive association between prostate cancer risk and carrying either the AT or TT genotype [odds ratio (OR) = 1.16, 95% confidence interval (CI) 0.79-1.69] in the MEC. This finding is in contrast to our previous results of ORs of 3.28 and 2.50 for the association between prostate cancer risk and the variant in African-American and Latino men, respectively; this can be accounted for by genotyping error in our earlier study. Meta-analysis of the published literature, including the current MEC data, shows a summary OR of 1.13 (95% CI 0.95-1.34) for the A49T variant with prostate cancer risk among sporadic, unselected cases. After evaluating more than 6000 cases and 6000 controls, there is little evidence of a role for the SRD5A2 A49T variant in prostate cancer risk. Overall, this report highlights the importance of rigorous genotyping quality control measures and replication efforts in genetic association studies.
类固醇5-α还原酶II型基因（SRD5A2）编码将睾酮（T）转化为活性更强的雄激素双氢睾酮的酶。SRD5A2基因中的一个非同义单核苷酸多态性A49T（rs9282858）与前列腺癌风险有关；然而，研究结果并不一致。1999年，我们报告了夏威夷-洛杉矶多民族队列（MEC）中，非洲裔美国人和拉丁裔人群中A49T变异与前列腺癌风险之间存在强关联。我们在此报告对MEC数据的更新分析，包括MEC的五个主要种族群体、增加的样本量、改进的基因分型技术以及对已发表文献的全面荟萃分析。我们发现MEC中前列腺癌风险与携带AT或TT基因型之间存在非统计学显著的正相关[比值比（OR）=1.16，95%置信区间（CI）0.79 - 1.69]。这一发现与我们之前的结果形成对比，之前在非洲裔美国人和拉丁裔男性中，前列腺癌风险与该变异之间的OR分别为3.28和2.50；这可以用我们早期研究中的基因分型错误来解释。对已发表文献（包括当前的MEC数据）进行荟萃分析表明，在散发性、未经过选择的病例中，A49T变异与前列腺癌风险的汇总OR为1.13（95%CI 0.95 - 1.34）。在评估了6000多例病例和6000例对照后，几乎没有证据表明SRD5A2 A49T变异在前列腺癌风险中起作用。总体而言，本报告强调了基因关联研究中严格的基因分型质量控制措施和重复验证工作的重要性。
