Influence of Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and N-acetyltransferase 2 (NAT2) Variants on Bladder Cancer Progression and Recurrence Rating: A Bosnian and Herzegovinian Case-Control Study

Introduction: It is suggested that bladder cancer (BC) development is linked to glutathione S-transferase (GST) enzymes. This study aimed to determine the correlation between glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase Theta 1 (GSTT1), and N-acetyltransferase 2 (NAT2) variants with BC progression and recurrence rating. Materials and methods: This study included 105 Bosnian and Herzegovinian subjects: 60 patients with histopathologically confirmed BC and 45 controls without urological diseases. GSTM1, GSTT1 (rs36631 and rs17856199, respectively), and NAT2 (rs1799929, rs1799930, and rs1799931) were investigated. Results: Both one- and five-year probabilities of progression were not significantly different in GSTM1 and NAT2 polymorphisms. One-year probability of progression was significantly higher in the GSTT1 T-- (null) than the T++ (wildtype) genotype (14.7% (±6.9) vs. 8.9% (±6.7), respectively; p=0.048). Five-year probability of progression was significantly higher in the GSTT1 T-- than the T++ genotype (39.4% (±14.7) vs. 25.5% (±16.6), respectively; p=0.045). THE GSTT1 T-- genotype was an independent predictor in the one-year probability of recurrence and progression (p=0.03 and p=0.01, respectively). GSTT1 T-- genotype and age were independent predictors for the five-year probability of recurrence (p=0.032 and p=0.04, respectively) as well as independent predictors of the five-year probability of progression (p=0.012 and p=0.03, respectively). Conclusions: The GSTT1 T-- genotype was an independent predictor in the one- and five-year probabilities of both recurrence and progression of BC. GSTT1 rs17856199 may be a significant factor in the development of tumors and the course of disease in Bosnian and Herzegovinian BC patients.