Genotypes of TNF-α, VEGF, hOGG1, GSTM1, and GSTT1: Useful determinants for clinical outcome of bladder cancer

To determine whether polymorphisms of tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), human 8-oxoguanine DNA glycosylase 1 (hOGG1), glutathione S-transferase-μ (GSTM1), and glutathione S-transferase-φ (GSTT1) are risk factors for bladder cancer among Koreans. We performed polymerase chain reaction-restriction fragment length polymorphism and multiplex polymerase chain reaction in blood genomic DNA of 153 patients with primary bladder cancer and 153 control subjects. GSTM1-negative, GSTT1-positive, and hOGG1 Ser326Ser and Ser326Cys genotypes are risk factors for bladder cancer (P = 0.020, P = 0.044, and P = 0.012, respectively). The cancer stage was significantly associated with the TNF-α genotype (GG versus GA and AA; P = 0.036). A notable correlation was observed between the VEGF genotype and grade (P = 0.015). In patients with superficial bladder cancer, the hOGG1 genotype was related to recurrence. The hOGG1 Ser326Ser and Ser326Cys genotypes were risk factors for superficial bladder cancer recurrence compared with the Cys326Cys genotype (P = 0.033, adjusted odds ratio 5.580, 95% confidence interval 1.145 to 27.183). Patients with the GSTM1-positive genotype were at a 3.3-fold increased risk of cancer progression compared with those with the GSTM1-negative genotype (P = 0.009, adjusted odds ratio 0.303, 95% confidence interval 0.123 to 0.745). Our data collectively suggest that these genetic polymorphisms may be useful as prognostic markers for bladder cancer in the clinical setting.