Department of Urology, Graduate School of Medicine, The University of Tokyo, Japan.
Clin Genitourin Cancer. 2011 Sep;9(1):46-52. doi: 10.1016/j.clgc.2011.04.004. Epub 2011 Jun 22.
We conducted present study to address whether the rs6983561 polymorphism, an established genetic marker for prostate cancer susceptibility, was a prognostic indicator. We genotyped 518 Japanese patients with prostate cancer and analysed their survival retrospectively. As a result, patients with the CA/CC genotype of rs6983561 survived significantly longer than those with the AA genotype (P = .033).
Genome-wide association studies have revealed several genetic variants at 8q24 that are associated with prostate cancer susceptibility. Rs6983561 (A/C) is a single-nucleotide polymorphism located at 8q24 that has been established as a genetic risk marker for prostate cancer susceptibility. The present study investigated the association between the rs6983561 polymorphism and prostate cancer mortality in a Japanese population.
The study examined 518 native Japanese male patients with sporadic prostate cancer. Germline DNA samples were obtained from all participants and genotyping of rs6983561 was performed using a TaqMan assay. Observation periods were from the date of diagnosis of prostate cancer to May 21, 2010. The Cox proportional hazards model was used to estimate the cause-specific survival (CSS) and the overall survival (OS).
Patients with the CA/CC genotype of rs6983561 survived significantly longer than those with the AA genotype. In a multivariate model, the hazard ratios (HRs) and 95% confidence intervals (CIs) of the CSS and the OS for the rs6983561 polymorphism were 2.438 (1.262 - 5.046, P = .007) and 1.957 (1.142 - 3.485, P = .014), respectively. When the analysis was restricted to subjects with metastatic disease, the HRs of the CSS and the OS were 3.353 (95% CI, 1.689 - 7.446; P = 3.76 x 10(-4)) and 3.361 (95% CI, 1.741 - 7.136; P = 1.70 x 10(-4)), respectively.
In the Japanese population examined in this study, the rs6983561 polymorphism at 8q24 was significantly associated with prostate cancer mortality, especially among patients with metastatic disease.
本研究旨在探讨 rs6983561 多态性（前列腺癌易感性的既定遗传标志物）是否为预后指标。我们对 518 例日本前列腺癌患者进行了基因分型，并回顾性分析了他们的生存情况。结果显示，rs6983561 多态性的 CA/CC 基因型患者的生存时间明显长于 AA 基因型患者（P=0.033）。
全基因组关联研究揭示了 8q24 上与前列腺癌易感性相关的几个遗传变异。rs6983561（A/C）是位于 8q24 的单核苷酸多态性，已被确立为前列腺癌易感性的遗传风险标志物。本研究在日本人群中调查了 rs6983561 多态性与前列腺癌死亡率之间的关系。
本研究纳入了 518 例散发性前列腺癌的日本男性患者。所有参与者均采集了种系 DNA 样本，并采用 TaqMan 法进行 rs6983561 基因分型。观察期从前列腺癌诊断之日至 2010 年 5 月 21 日。采用 Cox 比例风险模型估计特定原因的生存（CSS）和总生存（OS）。
rs6983561 的 CA/CC 基因型患者的生存时间明显长于 AA 基因型患者。在多变量模型中，rs6983561 多态性的 CSS 和 OS 的风险比（HR）和 95%置信区间（CI）分别为 2.438（1.262-5.046，P=0.007）和 1.957（1.142-3.485，P=0.014）。当分析仅限于转移性疾病患者时，CSS 和 OS 的 HR 分别为 3.353（95%CI，1.689-7.446；P=3.76x10(-4)）和 3.361（95%CI，1.741-7.136；P=1.70x10(-4)）。
在本研究中检查的日本人群中，8q24 上的 rs6983561 多态性与前列腺癌死亡率显著相关，尤其是在转移性疾病患者中。
