4.4 Article

The TERT locus genotypes of rs2736100-CC/CA and rs2736098-AA predict shorter survival in renal cell carcinoma

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.urolonc.2019.01.014

Keywords

Renal cell carcinoma; Prognostic factors; SNPs; TERT; Telomerase

Funding

  1. National Natural Science Foundation of China [81711530048, 81572515]
  2. Shandong Provincial Natural Science Foundation, China [2016ZDJS07A09]
  3. Swedish Cancer Society [CAN 2016/427]
  4. Cancer Society in Stockholm [171223]
  5. Stockholm County Council [2018-0183]
  6. Karolinska Institutet [2018-0183]
  7. Nanna Svartz Foundation [2017-00214]

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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 andRCCrisk. rs2736100-CC/CAand rs2736098-AA variants serve as independent predictors of a poor prognosis in RCC. Given that blood or even urinaryDNAcan be used to genotype these germline variants before treatment, these 2 SNPsmayserve as a potential marker for risk stratification. (C) 2019 Elsevier Inc. All rights reserved.

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