The risk of recurrence of breast cancer in the presence of deletion polymorphism of the GSTT1 and GSTM1 genes

Abstract

Objective: The aim of the study was to establish the relationship between the effectiveness of chemotherapy (CMT) in case of breast cancer and the risk of recurrence with polymorphism of glutathione-S-transferase (GSTT1, GSTM1) genes.Methods: The study involved 132 women having breast cancer diagnosed, aged 23 to 79 years (average age 48 ± 13 years). They received chemotherapy treatment (neoadjuvant (NACMT), adjuvant (ACMT)). The detection of deletion (null) genotypes GSTM1 and GSTT1 was carried out using multiplex PCR followed by analysis of the melting curves of the reaction products.Results: Statistically significant connection between the presence of a null genotype GSTM1-0 and a reduced risk of breast cancer recurrence in patients having stage III BC (RR = 0.721; 95% CI: 0.524-0.992, p = 0.034). At the same time, the precense of GSTT1-0 genotype didn't have statistically significant effect on the risk of recurrence (RR = 0.543; 95% CI: 0.274– 1.077, p = 0.015). However, the tendency of the prevalence of GSTT1 0/0 among patients without recurrnece of breast cancer persisted.Conclusions: The lack of activity of the GSTT1 or GSTM1 enzymes in carriers of null genotypes can lead to a decrease in detoxification capacity and, accordingly, to a longer circulation of active metabolites of medicine and reactive oxygen species. It prolongs the time of exposure of chemotherapy drugs on tumor cells. The functionally active enzymes may increase the risk of breast cancer recurrence due to rapid elimination of drugs.