Association of Polymorphisms in the Glutathione S-Transferase Theta-1 Gene with Cirrhosis and Hepatocellular Carcinoma in Brazilian Patients with Chronic Hepatitis C

Oxidative stress contributes to hepatitis C virus (HCV)–induced liver damage. Host genetic factors may be involved in progression of HCV infection. The present study was conducted to determine the influence of glutathione S-transferase (GST)-M1 and T1 gene polymorphisms during different stages of HCV infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The study population comprised 190 patients (47 with chronic hepatitis, 83 with cirrhosis (without HCC), and 60 with HCC). GSTM1 and GSTT1 gene polymorphisms were analyzed via multiplex polymerase chain reaction. The GSTT1-null genotype was more commonly detected in patients with cirrhosis (n = 17; 20.5%) and HCC (n = 13; 21.7%) than those with chronic hepatitis (n = 3; 6.4%). The differences in GSTT1-null genotype frequencies were significant for cirrhosis vs. chronic hepatitis (odds ratio, OR, 3.778 (95% confidence interval, CI, 1.045–13.659); p = 0.043) and HCC vs. chronic hepatitis (OR, 4.057 (95% CI, 1.083–15.201); p = 0.038) groups. However, the incidence of individual GSTM1-null or combined GSTM1/GSTT1 double-null genotypes did not vary significantly between the groups. Our collective findings support the utility of the GSTT1-null genotype as a useful biomarker for liver disease progression in Brazilian patients with chronic hepatitis C.

Individual and combined effects of GSTM1 and GSTT1 polymorphisms on colorectal cancer risk: an updated meta-analysis

Background. The presence or absence of glutathione S-transferase M1 gene (GSTM1) and glutathione S-transferase T1 gene (GSTT1) polymorphisms, and their combined effects have been suggested as a risk factor for colorectal cancer (CRC). However, the results are inconsistent. Objectives. An updated meta-analysis was performed to solve the controversy. Methods. Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were used. Results. Overall, the GSTM1 null genotype was associated with an increased CRC risk in Caucasians (odds ratio (OR) = 1.14, 95% confidence interval (CI): 1.05–1.23), Asians (OR = 1.19, 95% CI: 1.08–1.32), high-quality studies (OR = 1.12, 95% CI: 1.06–1.18). Moreover, the GSTM1 null genotype was also associated with an increased colon cancer risk (OR = 1.32, 95% CI: 1.16–1.51). The GSTT1 null genotype was also associated with an increased CRC risk in Asians (OR = 1.08, 95% CI: 1.02–1.15) and Caucasians (OR = 1.24, 95% CI: 1.09–1.41). Moreover, The GSTT1 null genotype was associated with an increased rectal cancer risk (OR = 1.13, 95% CI: 1.01–1.27, I2 = 8.3%) in subgroup analysis by tumor location. Last, the GSTM1 null/GSTT1 null genotype was associated with an increased CRC risk in Asians. Conclusion. This meta-analysis indicates that the GSTM1 and GSTT1 null genotypes are associated with increased CRC risk in Asians and Caucasians, and the GSTM1 null/GSTT1 null genotype was associated with increased CRC risk in Asians.