XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms and risk of clear cell renal cell carcinoma

Article type: Research Article

Authors: Loghin, Andrada^a | Bănescu, Claudia^{b; *} | Nechifor-Boila, Adela^a | Chibelean, Calin^c | Orsolya, Martha^c | Nechifor-Boila, Alin^c | Tripon, Florin^b | Voidazan, Septimiu^d | Borda, Angela^a

Affiliations: [a] Department of Histology, University of Medicine and Pharmacy Tirgu Mures, Romania | [b] Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, Romania | [c] Department of Urology, University of Medicine and Pharmacy Tirgu Mures, Romania | [d] Department of Epidemiology, University of Medicine and Pharmacy Tirgu Mures, Romania

Correspondence: [*] Corresponding author: Claudia Bănescu, Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania. Tel.: +40 265 215551 extension 184; Fax: +40 365 814927; E-mail:[email protected]

Abstract: INTRODUCTION: In the last decade, an increasing number of polymorphisms in DNA repair genes have been identified and their involvement in carcinogenesis was studied. Despite the fact that XRCC3 and XPD DNA repair genes association with several types of cancer was widely studied, their role in the development of clear cell renal cell carcinoma (CCRCC) has not been established in the European population. OBJECTIVE: The objective of this study was to investigate the association of XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms with the risk of CCRCC and the association between these genotypes and CCRCC histopathological prognostic factors (pathologic stage, Fuhrman grade, tumor diameter). METHODS: This study included 73 patients with CCRCC and 100 healthy individuals without cancer. We used the PCR-RFLP method to determine XRCC3 and XPD genotypes. RESULTS: The XPD 751 variant genotype (Lys/Gln) was more frequent in CCRCC patients than in healthy individuals (OR = 2.92, 95%CI: 1.47-5.79, p= 0.001). Regarding the XRCC3 Thr241Met/XPD Lys751Gln combined genotypes a significant difference was found between patients and controls for Thr/Thr+Lys/Gln (OR = 5.44, 95%CI: 2.09-14.15, p= 0.0003) and for Thr/Met+Gln/Gln (OR = 11.2, 95%CI: 1.95-100.4, p= 0.01).No association was found between any of the studied genotypes and histopathological prognostic factors of CCRCC. CONCLUSIONS: Our findings indicate that XPD Lys751Gln polymorphism may be a risk factor for CCRCC. Regarding the XRCC3 Thr241Met polymorphism, an association with CCRCC was found only in XRCC3 Thr241Met/XPD Lys751Gln combined genotypes.

Keywords: Gene polymorphisms, DNA repair genes, XRCC3, XPD, clear cell renal cell carcinoma

DOI: 10.3233/CBM-150558

Journal: Cancer Biomarkers, vol. 16, no. 2, pp. 211-217, 2016