Down Regulation in Glutathione S-Transferase Stimulate Oxidative Stress and Genetic Susceptibility of Human Breast Cancer

Abstract

Glutathione S-Transferase is an enzyme that catalyzed the formation of thio-ether conjugates between the endogenous tripeptide glutathione and xenobiotic compounds. Imbalance of glutathione level is observed in a variety of disease including breast cancer. In the present study we observed the alteration in the glutathione level and variation in glutathione S-transferase enzyme supergene family to influence susceptibility to breast cancer disease. Our study include 50 breast cancer tissues sample along with 25 ANCT control. The experiments were performed through high performance liquid chromatography to determine the endogenous glutathione level and multiplex PCR was used to determine GSTM1 & GSTT1 genotypes. The relationship between breast cancer and disease progression and histological grade were estimated by one way ANOVA and descriptive statisctics followed by spearman correlation {S.D±SEM, 95% CI (P<0.05)}. The study show decreased level of glutathione (GSHt P<0.05, GSH, GSSG P>0.05) in breast cancer tissue sample when compared to control, while no significance difference was occurred in GST (P>0.05) concentration when compared to control. In addition significance difference was observed when correlated histological grades {(grade II P<0.05) gradeII & III P>0.05)} with control subjects. We therefore, also investigated the role of GST genotypes to associate the role of this genotype in breast cancer. Genotyping study of GST show that the GSTM1 (P>0.05) null genotype was significantly associated with breast cancer and we found no association with breast cancer and GSTT1 (P<0.05) null genotype. In conclusion our study suggest that the dysregulation of glutathione level were associated with breast cancer and GSTM1 null genotype could be a useful marker for breast cancer prognosis.