Pharmacogenetic assessment of cytostatic therapy efficacy depending on the polymorphism of T1 and M1 glutathione-S-transferase genes in breast cancer patients

Abstract

Aim. To study the effect of deletion polymorphism of the GST genes (GSTT1, GSTM1) on chemotherapy (CT) efficacy in women diagnosed with breast cancer (BC) in the Primorsky Krai. Materials and methods. The study involved 132 women with breast cancer aged 23 to 79 years (mean age 48 ± 13 years) who received chemotherapy treatment. The detection of deletion (null) genotypes of GSTM1 and GSTT1 was carried out using multiplex PCR followed by an analysis of the melting curves of the reaction products. Results. Relapse-free survival (RFS) of BC patients with the “null” GSTT1 genotype was statistically significantly higher (116.7 months (9.6 years) versus 75.8 months (6.2 years)) than in patients with the “normal” GSTT genotype. Thus, in the case of the GSTT1“null” genotype, the risk of disease relapse decreased by 2.4 times (HR = 0.418, CI = 0.191–0.915, p = 0.024). Similar to GSTT1, the DFS of patients with the GSTM1 null genotype increased from 72.7 months (6 years) to 76.1 months (6.3 years). At the same time, the risk of disease relapse in carriers of the “null” GSTM1 genotype decreased by 1.7 times (HR = 0.596, CI = 0.369–0.964, p = 0.033) compared with that in carriers of the “normal” GSTM1 genotype. Conclusions. Deletion polymorphism of the GSTT1 and GSTM1 genes has a significant impact on chemotherapy efficacy in breast cancer patients. Carriers of “null” genotypes demonstrated a higher RFS and a lower risk of developing disease relapse. Further research in this direction and validation of the data obtained may contribute to individualizing the treatment of breast cancer patients, optimizing chemotherapy regimens, and reducing the number of adverse events.