title: Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology.
abstract: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase and plays a key role in telomere restitution and gene regulation. Evidence suggests that hTERT is linked with the risk and progression of several malignancies, but there are no comprehensive data in renal cell carcinoma (RCC). In this case-control study, we assessed seven polymorphic hTERT gene variants (MNS16A, rs2736100, rs2736098, rs7726159, rs2853677, rs13172201, and rs10069690), hTERT serum levels, and the telomere length of 663 individuals, including 243 with clear cell RCC and 420 age- and gender-matched healthy controls. The SL and SS genotypes of MNS16A were associated with a decreased risk for RCC on the multivariable logistic regression analysis (SL-OR 0.72, SS-OR 0.37, P < 0.001). The GG genotype of rs2736098 was associated with a decreased risk for RCC compared with AA (OR 0.18, P < 0.001). Both telomere length and hTERT serum levels increased with every G allele in rs2736098 (P = 0.008). Pretherapeutic hTERT serum levels were higher in patients with advanced tumor stages (P = 0.037) and distant metastases (P = 0.006). Rs2736100, rs7726159, rs2853677, rs13172201, and rs10069690 were not linked with RCC risk, and none of the polymorphisms was associated with RCC pathology. In conclusion, the polymorphic number of tandem repeats in hTERT (MNS16A) and rs2736098 may be linked with the risk for RCC. Rs2736098 may have an important role in telomere length restitution and serum hTERT levels may represent a novel biomarker for RCC. © 2015 Wiley Periodicals, Inc.
authors: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Michela
authors: M
authors: de Martino
authors: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Christopher
authors: C
authors: Taus
authors: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Ilaria
authors: I
authors: Lucca
authors: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Sebastian L
authors: SL
authors: Hofbauer
authors: Clinical Institute of Pathology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Andrea
authors: A
authors: Haitel
authors: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Shahrokh F
authors: SF
authors: Shariat
authors: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria. tobias.klatte@gmx.de.
authors: Tobias
authors: T
authors: Klatte
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000097:blood* / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D059505:Telomere Homeostasis
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: hTERT; polymorphism; renal cell carcinoma; telomerase activity; telomere length