Nibrin (NBS1) is a protein involved in the maintenance of genomic stability and in DNA repair mechanisms. The NBS1 E185Q polymorphism (rs1805794) has been investigated in several studies, including its influence in the pathogenesis of renal cell carcinoma (RCC), although its prognostic value is still not determined for these patients. The purpose of the present work was to determine the role of NBS1 E185Q polymorphism as a prognostic factor/genetic marker of survival in patients with RCC. We conducted a hospital-based study analyzing 172 caucasian patients with histopathological diagnosis of RCC, for which polymorphism genotyping was performed by TaqMan(®) Allelic Discrimination methodology. In this study, we have found that male patients, non-metastatic at diagnosis and NBS1 C allele carriers (GC/CC) showed a lower 5-years survival when compared with GG genotype patients (P = 0.045). Furthermore, for carriers of low-activity NBS1 C allele, multivariate Cox regression analysis revealed almost a fourfold increase in risk of death at 5 years, after adjustment for age, histological type, Fuhrman's grade, tumor size and vascular permeation (HR 3.92; 95 % CI 1.33-11.57; P = 0.013). There were no statistically significant differences between the NBS1 E185Q genotypes and the assessed patients' clinical-pathological characteristics. Our results demonstrate for the first time the impact of NBS1 E185Q polymorphism in RCC prognosis suggesting that, for RCC male patients non-metastatic at diagnosis, this polymorphism might be a putative genetic marker in the clinical outcome.
Keywords: NBS1; Polymorphism; Prognosis; Renal cell carcinoma; Survival.