RESUMO
Polymorphisms in the glutathione transferase enzymes (GSTs) genes have been associated with susceptibility to develop breast cancer (BC), but few are known regarding its role on this disease prognosis and impact on antioxidant status. This study evaluated the polymorphisms of GSTM1 and GSTT1 genes and their relationship with BC susceptibility and prognostic, as well as its impact on plasma reduced glutathione (GSH) levels. The present study included 121 women with invasive ductal BC and 151 healthy controls. Polymorphisms analyses were performed using the polymerase chain reaction (PCR) technique and GSH levels were measured with the Ellman's reagent. GSTT1 (OR 1.29; p = 0.39) and GSTM1 (OR 1.03; p = 0.91) polymorphisms did not show any association with BC susceptibility. The mean concentration values in nmol/L of GSH were 20.37 ± 5.82 for patients with null genotypes for both genes, 19.75 ± 3.47 for null GSTT1, 17.22 ± 1.35 for active GSTT1, 18.82 ± 1.96 for absent GSTM1, and 16.59 ± 1.66 for active GSTM1, but no significance was found. Therefore, it can be concluded that the behavior of these polymorphisms concerning BC might be not only related to the absence of enzymatic expression but may also be related to the body's response with its antioxidant mechanisms and it should be further studied.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Adulto , Idoso , Antioxidantes/metabolismo , Brasil/epidemiologia , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Estudos de Associação Genética , Glutationa/sangue , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , PrognósticoRESUMO
Breast cancer (BC) is a heterogeneous and multifactorial disease. The system formed by glutathione-S-transferases (GSTs) acts to protect the organism against the oxidative stress generated by xenobiotics and their active products. Glutathione transferase mu 1 (GSTM1) and glutathione transferase theta 1 (GSTT1) present null polymorphic variants by complete deletion. The absence of these enzymes may influence the susceptibility to several diseases such as BC. This study aimed to systematically review and investigate the existence of a possible correlation between the presence/absence of these genetic variants and the development of BC and their influence in chemotherapy response. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used, and the searches were performed in the portal of the Virtual Health Library (VHL) and the PubMed, resulting in 21 articles. It is clear that most studies revealed a risk association between the deletion of GSTM1 and/or GSTT1 and the development and/or prognosis of BC.Moreover, it should be noted that these results of risk association were found in large part in the populations of the Americas and Europe, followed by Asians. Regarding the response to treatment, protective associations were found in the presence of GSTM1 deletion. However, due to the inconclusive results of many studies, further analysis in this area is required.
