Glutathione peroxidase 1 gene polymorphism and risk of recurrence in patients with superficial bladder cancer

Abstract

Objectives To investigate the potential of genetic polymorphism (Pro198Leu) in the human glutathione peroxidase 1 ( hGPX1) gene as a biologic marker predictive of bladder cancer recurrence. Given the high propensity for superficial bladder cancer recurrence, biologic markers that are predictive of recurrence may provide additional helpful information in bladder cancer treatment. To date, few valuable molecular markers have been closely associated with bladder cancer recurrence. Methods In this ongoing prospective study, we investigated the potential of genetic polymorphism (Pro198Leu) in the hGPX1 gene, whose protein product is an important metabolic enzyme, as a recurrence predictor. Results This study included 224 patients with superficial bladder cancer. During a median follow-up of 25.2 months, 138 (61.6%) of the 224 patients experienced disease recurrence. Patients with the hGPX1 wild type had marginally shorter recurrence-free survival compared with those with the hGPX1 variant genotype (log-rank test, P = 0.066). The difference was even greater in whites (log-rank test, P = 0.036). When we performed multivariate analysis using Cox proportional hazards model, we detected a borderline protective role for the hGPX1 variant genotype in recurrence, with a hazard ratio of 0.71 (95% confidence interval 0.48 to 1.05). The protective association was even stronger in whites (hazard ratio 0.63, 95% confidence interval 0.42 to 0.96). Conclusions Our findings suggest that a genetic polymorphism in the hGPX1 gene may serve as a molecular marker for monitoring bladder cancer recurrence.