Genotypes of TNF-alpha, VEGF, TGF-beta1, hOGG1, GSTM1 and GSTT1: Useful Determinants for the Clinical Outcome of Bladder Cancer / 대한비뇨기과학회지

ABSTRACT

PURPOSE: Detoxification enzymes, cytokines and the gene repair systems are involved in carcinogenesis, cancer recurrence and the progression of human urinary bladder cancer. This study was designed to evaluate the clinical influences of genetic polymorphism of the TNF-alpha, VEGF, TGF-beta1, hOGG1, GSTM1 and GSTT1 genes on bladder cancer. MATERIALS AND METHODS: To determine whether the polymorphisms of TNF-alpha, VEGF, TGF-beta1, hOGG1, GSTM1 and GSTT1 are risk factors for bladder cancer among Koreans, PCR-based restriction fragment length polymorphism (RFLP) and multiplex PCR were performed on genomic blood DNA. RESULTS: Multiple logistic analyses revealed that the GSTM1 (negative) and hOGG1 (Ser326Ser and Ser326Cys) genotypes were risk factors for the development of bladder cancer (p=0.030, AOR=1.690, 95% CI=1.052-2.714 and p=0.020, AOR=1.988, 95% CI=1.112-3.546, respectively). In patients with superficial bladder cancer, the hOGG1 (Ser326Ser and Ser326Cys versus Cys326Cys) and TGF-beta1 (CC versus CT and TT) genotypes were significantly correlated with a recurrence (p=0.031, AOR=6.034, 95% CI= 1.185-30.733, and p=0.031, AOR=0.163, 95% CI=0.031-0.851, respectively). Disease progression in patients with bladder cancer was associated with the GSTM1 genotype (positive versus negative) (p=0.018, AOR=0.325, 95% CI=0.128-0.827). CONCLUSIONS: Our data collectively suggest that the hOGG1, TGF-beta1 and GSTM1 genotypes are closely correlated with the recurrence and progression of bladder cancer, and may, therefore, be useful as prognostic markers for bladder cancer in a clinical setting.