Aim: The aim of this study was to evaluate specific role of glutathione S-transferase P1 (GSTP1) gene variants as determinants of ccRCC risk in patients with advanced tumor stage (pT3 and pT4). Furthermore, we evaluated the effect of GSTP1 gene variants on postoperative prognosis in these patients.
Introduction: Renal cell carcinoma (RCC) accounts for up to 90% of malignant kidney tumors with clear renal cell carcinoma (ccRCC) being the most frequent and the most aggressive subtype of sporadic RCC in adults. Unfortunately, most RCCs are asymptomatic in early stages, whereas symptomatic RCC correlates with aggressive histology and advanced disease. Aside from known risk factors for RCC, evidence suggest that the development of RCC can be partially explained by genetic variations among the populations. Highly polymorphic cytosolic glutathione S-transferases are known to be involved in both the development and the progression of renal cell carcinoma.
Methods: GSTP1 genotype was determined in 99 ccRCC patients and 326 matched-controls by qPRC method, using TaqMan® SNP Genotyping Assay. The risk for disease was computed by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression analysis Furthermore, overall survival was analyzed as well by Kaplan-Meier method and Cox proportional hazard regression model.
Results: GSTP1-variant genotype was associated with 5-fold increased risk for ccRCC in comparison with GSTP1-wild type genotype (p<0.001). Moreover, survival analysis clearly indicated shorter overall survival in ccRCC patients with GSTP1-variant genotype, however without reaching statistical significance (p=0.166). Additionally, ccRCC patients with GSTP1-variant genotype had a 7-fold higher hazard ratio (p=0.177), compared to the carriers of GSTP1-wild type genotype.
Conclusion: GSTP1-variant genotype contributed independently towards the risk of ccRCC in our patients. Moreover, GSTP1-variant genotype is associated with poor postoperative prognosis in ccRCC.