Department of Urology, Peking University Third Hospital, Beijing 100191, PR China.
Department of Pathology, Peking University Third Hospital, Beijing 100191, PR China.
Urol Oncol. 2019 May;37(5):301.e1-301.e10. doi: 10.1016/j.urolonc.2019.01.014. Epub 2019 Feb 7.
The single nucleotide polymorphisms (SNPs) at the TERT rs2736100 and rs2736098 are associated with multicancer susceptibility, however, published findings regarding renal cell carcinoma (RCC) risk are conflicting. In addition, the potential of these SNPs to predict outcomes in RCC remains unclear. The present study is designed to address these questions.
We recruited 343 patients with RCC and ethnic-/sex-matched healthy controls. TERT rs2736100 and rs2736098 SNPs were analyzed, and their relationships with relapse/survival were evaluated using univariate or multivariate Cox regression.
The genotype distribution did not significantly differ between RCC patients and healthy controls. RCC patients carrying the rs2736100-CC/CA variants had significantly shorter progression-free and overall survival (PFS and OS) than did those AA-carriers (P = 0.009 and 0.032, respectively), while the rs2736098-AA variant was associated with shorter PFS and OS (P = 0.008 and 0.017, respectively). Multivariate analyses showed that rs2736100-CC/CA and rs2736098-AA predicted shorter PFS and OS independently of other established prognostic variables in RCCs. Furthermore, patients carrying both rs2736100-CC/CA and rs2736098-AA had shortest PFS and OS (P = 0.003 and 0.013, respectively) and the hazard ratio of relapse was 7.2 (95% confidence interval: 2.0-26.1).
There is no significant association between rs2736100/rs2736098 SNPs and RCC risk. rs2736100-CC/CA and rs2736098-AA variants serve as independent predictors of a poor prognosis in RCC. Given that blood or even urinary DNA can be used to genotype these germline variants before treatment, these 2 SNPs may serve as a potential marker for risk stratification.
端粒酶逆转录酶（TERT）rs2736100 和 rs2736098 单核苷酸多态性（SNPs）与多种癌症易感性相关，但有关肾细胞癌（RCC）风险的研究结果存在争议。此外，这些 SNPs 预测 RCC 患者结局的能力尚不清楚。本研究旨在解决这些问题。
我们招募了 343 例 RCC 患者和种族/性别匹配的健康对照者。分析了 TERT rs2736100 和 rs2736098 SNPs，使用单变量或多变量 Cox 回归评估它们与复发/生存的关系。
RCC 患者和健康对照组的基因型分布无显著差异。携带 rs2736100-CC/CA 变异的 RCC 患者无进展生存期（PFS）和总生存期（OS）明显短于携带 AA 变异的患者（P=0.009 和 0.032），而 rs2736098-AA 变异与较短的 PFS 和 OS 相关（P=0.008 和 0.017）。多变量分析显示，rs2736100-CC/CA 和 rs2736098-AA 独立于 RCC 中其他已建立的预后变量预测较短的 PFS 和 OS。此外，同时携带 rs2736100-CC/CA 和 rs2736098-AA 的患者 PFS 和 OS 最短（P=0.003 和 0.013），复发的危险比为 7.2（95%置信区间：2.0-26.1）。
rs2736100/rs2736098 SNPs 与 RCC 风险无显著相关性。rs2736100-CC/CA 和 rs2736098-AA 变体是 RCC 预后不良的独立预测因子。鉴于在治疗前可以使用血液甚至尿液 DNA 对这些种系变体进行基因分型，这两个 SNPs 可能成为风险分层的潜在标志物。
