Glutathione S-Transferase Mu And Theta Polymorphisms And Renal Cell Carcinoma Susceptibility

Objective: The glutathione S-transferases(GSTs) are involved in the metabolism of numerous potential environmental carcinogens. However, it was reported that in certain instances, the glutathione conjugate formed from catalytic reaction of GSTT1 is more reactive than the parent compound. As the GSTTI protein is highly expressed in human kidney, it would seem important to establish whether polymorphism of GSTTI is associated with an increased risk of renal cell carcinoma(RCC). The case-control study was designed to test for an association between genetic polymorphism of GSTM1 and GSTTI and the risk of sporadic RCC in Chinese population. Methods:1. Genomic DNA of WBC was obtained from 48 patients with RCC which had received surgical therapy;2. Genomic DNA of WBC was obtained from 60 controls of Chinese who had almost the same components of age, gender and smoke history;3. We used multiplex PCR to investigate the genotypes of GSTM 1 and GSTT 1 both in cases and controls;4. All the statistical analyses were performed using statistical software to contrast the different frequency of genotypes between cases and controls, further more, to test for an association between genetic polymorphism of GSTM 1 and GSTT 1 and the risk of sporadic RCC.Results:1. The frequency of GSTMl null genotype was 45.8% in cases and 50.0 % in controls with an adjusted odds ratio(OR) 0.98[95% confidence interval (CI), 0.79 — 1.74; P>0. 05]. The GSTM 1 polymorphisms did not show any significant association with RCC.2. The frequency of GSTT1 null gene type was 62. 5% in cases and 41. 7 % in controls with an adjusted odds ratio(OR) 1.70[95% confidence interval (CI), 1.12-2.52; P<0. 05]. Our results showed that the GSTT 1 null genotype was associated with the increase of one and a half risk of RCC.3. The frequency of GSTT1 null combined with GSTMl null gene type was29. 1 % in cases and 16.7% in controls with an adjusted odds ratio(OR) 2.06[95% confidence interval (CI), 1.21—4.05; P<0.05]. Our results showed that the GSTT 1 null combined with GSTMl null genotype highly increase the risk of RCC.4. The frequency of GSTT1 ( + ) combined with GSTMl ( + ) gene type was20. 8 % in cases and 25% in controls with an adjusted odds ratio(OR) 0. 83[95% confidence interval (CI), 0.56 — 1.21; P>0. 05]. Our results showed that the GSTT 1 ( + ) combined with GSTMl ( + ) genotype did not show any significant association with RCC.5. The frequency of GSTMl ( + ) combined with GSTT1 (-) gene type was33. 3 % in cases and 25% in controls with an adjusted odds ratio(OR) 1.35[95% confidence interval (CI), 0.90 — 2.17; P>0. 05]. Our results showed that the GSTT 1 ( + ) combined with GSTMl (-) genotype did not show any significant association with RCC.6. The frequency of GSTMl (-) combined with GSTT1 ( + ) gene type wasl6. 7 % in cases and 33.3% in controls with an adjusted odds ratio(OR) 0.47[95% confidence interval (CI), 0.32-0.75; P<0.05]. Our results showed that the GSTT 1 (+) combined with GSTMl (-) genotype may reducethe risk of RCC. Conclusions:1. The timid association between GSTMl null genotype and RCC risk in this population-based study suggested that the activity of GSTMl may not protect against RCC. These data demonstrated a timid association between genetic polymorphism of GSTMl and RCC risk.2. The significant association between GSTT1 null genotype and RCC risk in this population-based study suggested that the activity of GSTT1 protect against RCC. Therefore, individuals with GSTT1 null genotype may have a higher risk of RCC, especially in combination with GSTMl null genotype. Individuals with GSTT1 (+) genotype may have a lower risk of RCC. These data demonstrated a significant association between genetic polymorphism of GSTT1 and RCC risk...