Análise dos polimorfismos por deleção de GSTM1 e GSTT1 e níveis de glutationa em pacientes com carcinoma mamário: suscetibilidade e prognóstico

Abstract

Breast cancer is a heterogeneous disease of worldwide incidence and is considered a public health issue. External environmental factors, generically called xenobiotics, have a direct impact on the development and progression of this disease. The metabolization of xenobiotics and their byproducts ensures the elimination of compounds that could be harmful to the body and this action is also performed by the glutathione-S-transferase enzymes (GSTs). The genes glutathione transferase mu 1 (GSTM1) and glutathione transferase theta 1 (GSTT1) belong to the mu and theta classes, respectively. Individuals with polymorphic variants of GSTs are less efficient in detoxifying metabolites from drugs or carcinogens and, consequently, these individuals may be more susceptible to the development of diseases such as cancer. Therefore, this study aimed to evaluate polymorphisms by deletion of GSTM1 and GSTT1 and glutathione levels in patients with breast cancer and their clinicopathological correlations. A total of 121 women with invasive ductal breast cancer (CDI) and 151 women free of neoplasia participated in the study. DNA extraction of patients was performed by Salting out and of control women by the Mini Spin Plus Extraction Kit (BioPur, Curitiba, Paraná, BR). Polymorphism analysis was performed using the Multiplex polymerase chain reaction (PCR) technique. Glutathione dosages were performed with Ellman's reagent from the patients' plasma aliquots. According to the case-control study, the GSTT1 and GSTM1 polymorphisms do not seem to be candidates for markers of susceptibility to breast cancer. In addition, they did not show prognostic markers when correlated with disease parameters. Significant results were obtained between the presence of GSTT1 and a reduced concentration of GSH in patients with a history of chronic stress. There was also significance between the double positive genotype and an increase in GSH in the presence of angiolymphatic emboli, as well as significance between the double deleted genotype and a high ki67 value (> 14%). These results show that GSH has a different behavior in the presence or absence of these genes. This study is expected to contribute to the development of additional studies, taking into account the need to establish new markers for this neoplasm, given its considerable prevalence among women.