Genetic polymorphisms of CYP17A1 in steroidogenesis pathway are associated with risk of progression to castration-resistant prostate cancer in Japanese men receiving androgen deprivation therapy
Genetic polymorphisms of CYP17A1 in steroidogenesis pathway are associated with risk of progression to castration-resistant prostate cancer in Japanese men receiving androgen deprivation therapy
复制标题
DOI：
10.1007/s10147-012-0430-8
复制
发表时间：
2013-08-01
影响因子：
3.3
通讯作者：
Nonomura, Norio
中科院分区：
文献类型：
--
作者：
Yamada, Takeshi;Nakayama, Masashi;Nonomura, Norio
激素消融治疗是前列腺癌的标准治疗；然而，对治疗的反应持续时间存在很大的个体差异。在这项回顾性多中心研究中，我们调查了甾体激素发生相关基因的遗传多态性变异与日本患者在雄激素剥夺治疗后发展为去势抵抗性前列腺癌（CRPC）的风险之间的关系。214名接受雄激素剥夺治疗的日本前列腺癌患者参加了这项研究。我们研究了来自8个甾体生成相关基因的22个单核苷酸多态性（SNPs）。采用基于聚合酶链反应（PCR）的方法检测snp。根据激素治疗中位持续时间进展为CRPC的病例对照状态，对该队列中不同基因型进行分析。采用logistic回归方法对患者特征进行调整。采用logistic回归方法后，进行Cox回归分析，并进行Kaplan-Meier分析和log-rank分析。在logistic回归分析中，CYP17A1基因的4个遗传多态性rs743572、rs6162、rs6163和rs1004467与CRPC进展风险显著相关（p < 0.05）。对这些snp的Cox回归分析显示，进展为CRPC的风险与rs743572基因型相关（p = 0.02，优势比[OR] 0.43, 95%可信区间[CI] 0.22-0.85）。CYP17A1基因的遗传背景可能影响雄激素剥夺治疗后前列腺癌向CRPC的进展。
Hormone ablation therapy is the standard therapy for prostate cancer; however, there are large individual differences in the duration of response to the therapy. We investigated, in this retrospective multicenter study, the association between genetic polymorphic variations in steroidogenesis-related genes and the risk of progression to castration-resistant prostate cancer (CRPC) in Japanese patients after androgen deprivation therapy.Two hundred and fourteen Japanese patients with prostate cancer who were receiving androgen deprivation therapy were enrolled in this study. We investigated 22 single-nucleotide polymorphisms (SNPs) from 8 genes related to steroidogenesis. The SNPs were assayed by polymerase chain reaction (PCR)-based methods. The different genotypes in this cohort were analyzed according to a case-control status of progression to CRPC at the median duration of hormonal therapy. A logistic regression method with adjustments for patients' characteristics was applied for the analysis.After applying the logistic regression method, we performed Cox regression analysis, following Kaplan-Meier and log-rank analyses.In the logistic regression analysis four genetic polymorphisms, rs743572, rs6162, rs6163, and rs1004467, in the CYP17A1 gene were significantly associated with a risk of progression to CRPC (p < 0.05). Cox regression analysis for these SNPs showed an association of risk of progression to CRPC with the rs743572 genotype (p = 0.02, odds ratio [OR] 0.43, 95 % confidence interval [CI] 0.22-0.85).The genetic backgrounds for CYP17A1 genes could influence the progression of prostate cancer to CRPC after androgen deprivation therapy.