Povezanost polimorfizama SOD2 i GST gena sa rizikom za nastanak i prognozom papilarnog karcinoma bubrežnog parenhima

Abstract

Introduction: Redox imbalance is an important factor in both carcinogenesis and progression of renal cell carcinoma. Numerous studies are focused on finding potential biomarkers that can aid in early detection, as well as in monitoring disease progression. Among the candidates there are genes coding for antioxidant enzymes - superoxide dismutase 2 (SOD2) and glutathione S -transferase (GST). Aim: This study aims to assess the role of SOD2 and GST genes polymorphisms as risk biomarkers for papillary renal cell carcinoma (pRCC), along with their impact on the survival of these patients. Material and methods: This study included 39 patients and 336 controls. The following polymorphisms were determined by appropriate PCR methods: SOD2 (rs4880), GSTA1 C69T, GSTM1, GSTT1, and GSTP1 (rs1695) . ELISA method was used to measure 8-hydroxy-2'-deoxyguanosine (8-OHdG) and benzo(a)pyrene diol epoxide (BPDE)-DNA adducts plasma level. The effect of the polymorphisms on postoperative prognosis was examined using the available survival data. Results: There was no significant difference in the distribution of SOD2, GSTA1, GSTM1, and GSTT1 gene variants between patients and controls (p > 0.05). However GSTP1 variant (GSTP1 * IleVal + ValVal) genotype was statistically significantly more frequent in patients compared to controls (p < 0.05). Similarly, carriers of GSTP1 variant genotype were at significantly higher risk of developing carcinoma compared to carriers of GSTP1 reference genotype (OR = 16.103, 95% IP = 2.036 - 127.398). There was no association between the level of both 8-OHdG and BPDE-DNA adducts, and different genotypes (p > 0.05). The investigated polymorphisms did not show any prognostic significance (p > 0.05). Conclusion: These results indicate that the GSTP1 variant genotype was related to an increased risk of papillary renal cell carcinoma development. In order to fully understand the effect of investigated polymorphisms as a potential risk and prognostic biomarkers of this cancer, further research with a bigger sample size and longer follow-up are required.