Background. Breast cancer (BC) refers to multifactorial polygenic diseases that occur as a result of the combined interaction of genetic and environmental factors. Glutathione-mediated detoxification is of key importance in ensuring the resistance of body cells to the damaging effect of xenobiotics.Objective: to study the prevalence of deletion polymorphisms of the GSTM1 and GSTT1 genes and to establish their influence on the formation of cancer risk in patients with BC in the Primorye region (Russia).Materials and methods. The study involved 176 women with BC, aged 23 to 79 years (mean age 48 ± 13 years) and 66 conditionally healthy individuals without cancer. The detection of deletion (null) genotypes of the GSTM1 and GSTT1 was carried out using multiplex PCR followed by analysis of the melting curves of the reaction products.Results. The frequency of GSTT1-0 genotype among BC patients was higher than in the control group (14.77 % versus 6.06 %), significantly exceeding the indicators in the control group by more than 2.5 times (p <0.1), indicating an association between the carriage of the GSTT1-0 genotype and the risk of developing BC. At the same time, the frequencies of the GSTM1-0 genotype in the study groups were comparable; no statistically significant association with the risk of developing BC was found.Conclusions. Homozygous deletion of GSTT1 (GSTT1-0) can potentially be considered as a low-penetrant risk factor for developing BC in the population of Primorye region.
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.
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