Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
PLoS One. 2012;7(7):e41219. doi: 10.1371/journal.pone.0041219. Epub 2012 Jul 23.
Several genome-wide association studies (GWAS) have been conducted to identify the common single nucleotide polymorphisms (SNPs) that influence the risk of prostate cancer. It was hypothesized that some prostate cancer-associated SNPs might relate to the clinical outcomes in patients treated for prostate cancer using androgen-deprivation therapy (ADT). A cohort of 601 patients who have received ADT for prostate cancer was genotyped for 29 SNPs that have been associated with prostate cancer in Cancer Genetic Markers of Susceptibility GWAS, and within the genes that have been implicated in cancer. Prognostic significance of these SNPs on the disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model. Three SNPs, namely CASP3 rs4862396, BMP5 rs3734444 and IRS2 rs7986346, were found to be closely associated with the ACM (P≤0.042), and BMP5 rs3734444 and IRS2 rs7986346 were also noted to be significantly related to the PCSM (P≤0.032) after adjusting for the known clinicopathologic predictors. Moreover, patients carrying a greater number of unfavorable genotypes at the loci of interest had a shorter time to ACM and PCSM during ADT (P for trend <0.001). Our results suggest that CASP3 rs4862396, BMP5 rs3734444 and IRS2 rs7986346 may affect the survival in patients after ADT for prostate cancer, and the analysis of these SNPs can help identify patients at higher risk of poor outcome.
几项全基因组关联研究（GWAS）已经进行，以确定影响前列腺癌风险的常见单核苷酸多态性（SNP）。有人假设，一些与前列腺癌相关的 SNP 可能与接受雄激素剥夺疗法（ADT）治疗前列腺癌的患者的临床结局有关。对接受 ADT 治疗的 601 例前列腺癌患者进行了基因分型，检测了与癌症易感性 GWAS 中的前列腺癌相关的 29 个 SNP，以及与癌症相关的基因中的 SNP。通过 Kaplan-Meier 分析和 Cox 回归模型评估这些 SNP 对 ADT 后疾病进展、前列腺癌特异性死亡率（PCSM）和全因死亡率（ACM）的预后意义。发现三个 SNP（CASP3 rs4862396、BMP5 rs3734444 和 IRS2 rs7986346）与 ACM 密切相关（P≤0.042），BMP5 rs3734444 和 IRS2 rs7986346 也与 PCSM 显著相关（P≤0.032），调整了已知的临床病理预测因素后。此外，在感兴趣的基因座携带更多不良基因型的患者在 ADT 期间 ACM 和 PCSM 的时间更短（趋势 P<0.001）。我们的研究结果表明，CASP3 rs4862396、BMP5 rs3734444 和 IRS2 rs7986346 可能影响 ADT 后前列腺癌患者的生存，分析这些 SNP 有助于识别预后不良风险较高的患者。
