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

Urol Oncol. 2019 May;37(5):301.e1-301.e10. doi: 10.1016/j.urolonc.2019.01.014. Epub 2019 Feb 7.

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.

Keywords: Abbreviations: CI, confidence interval; HC, healthy control; HR, hazard ratio; OR, odds ratio; OS, overall survival; PFS, progression-free survival; Prognostic factors; RCC, renal cell carcinoma; Renal cell carcinoma; SNP, single nucleotide polymorphism; SNPs; TERT; TERT, telomerase reverse transcriptase; Telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality*
  • Female
  • Genotype
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Survival Rate
  • Telomerase / genetics*

Substances

  • TERT protein, human
  • Telomerase