This study was designed to investigate the association of genetic polymorphisms of cytochrome P450 subtype 2E1 (CYP2E1) and glutathione S-transferase mu 1 (GSTM1) with susceptibility to antituberculosis drug-induced hepatotoxicity (ADIH) in Chinese tuberculosis patients. All patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Genomic DNA from 104 patients with ADIH and 111 without ADIH was analysed for the frequency of CYP2E1 RsaI and GSTM1 RsaI genotypes by polymerase chain reaction and restriction fragment length polymorphism. The association of polymorphisms with susceptibility to ADIH was calculated using the chi(2)-test and logistic regression analysis. The CYP2E1 RsaI polymorphisms were significantly associated with ADIH and the c1/c1 genotype was an independent risk factor for ADIH. Compared with the GSTM1 RsaI present genotype, the GSTM1 RsaI null genotype tended to increase susceptibility to ADIH, but the association with ADIH was not significant. The results indicate that CYP2E1 RsaI genotype c1/c1 is a potential risk factor for ADIH in the Chinese population. The tendency of the GSTM1 RsaI null genotype to increase susceptibility to ADIH needs further study.
ABSTRACT. The aim of this study was to evaluate the role of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms in the clinical response to chemotherapy and treatment outcome of patients with breast cancer. A total of 262 subjects were randomly selected from among patients with a histologically confirmed breast cancer. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Our study found that the null genotype of GSTM1 was associated with a better response to chemotherapy, and the odds ratio [95% confidence interval (CI)] was 1.78 GST polymorphisms and breast cancer prognosis (1.03-3.08). In the Cox proportional hazard model, the hazard ratio (95%CI) for overall survival (OS) in patients carrying the null genotype of GSTM1 was 0.57 (0.32-0.98) using the non-null genotype as the reference variable. However, we observed no significant association between the GSTT1 and GSTP1 polymorphisms and response to chemotherapy and OS in patients with breast cancer. In conclusion, our study found that the GSTM1 polymorphism plays an important role in influencing the chemotherapy response and OS in patients with breast cancer.
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