Runzhuo Ma1, Cheng Liu1, Min Lu2, Xiaotian Yuan3, Guanghui Cheng4, Feng Kong4, Jian Lu1, Klas Strååt5, Magnus Björkholm5, Lulin Ma6, Dawei Xu5. 1. Department of Urology, Peking University Third Hospital, Beijing 100191, PR China. 2. Department of Pathology, Peking University Third Hospital, Beijing 100191, PR China. 3. Department of Medicine and Center for Molecular Medicine (CMM), Karolinska Institutet and Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. Electronic address: Xiaotian.Yan@ki.se. 4. Central Research Laboratory, the Second Hospital of Shandong University, Jinan 250033, PR China. 5. Department of Medicine and Center for Molecular Medicine (CMM), Karolinska Institutet and Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. 6. Department of Urology, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: malulinpku@163.com.
Abstract
OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVES: The single nucleotide polymorphisms (SNPs) at the TERTrs2736100 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. PATIENTS AND METHODS: We recruited 343 patients with RCC and ethnic-/sex-matched healthy controls. TERTrs2736100 and rs2736098 SNPs were analyzed, and their relationships with relapse/survival were evaluated using univariate or multivariate Cox regression. RESULTS: The genotype distribution did not significantly differ between RCCpatients and healthy controls. RCCpatients 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). CONCLUSIONS: 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.
Authors: Neeraj Agarwal; Sebastien Rinaldetti; Bassem B Cheikh; Qiong Zhou; Evan P Hass; Robert T Jones; Molishree Joshi; Daniel V LaBarbera; Simon R V Knott; Thomas R Cech; Dan Theodorescu Journal: Proc Natl Acad Sci U S A Date: 2021-09-21 Impact factor: 11.205