Русский
GSTT1 and GSTM1 deletion polymorphism as a predictor of response to hormonal therapy for breast cancer
DOI: https://dx.doi.org/10.18565/pharmateca.2023.11.60-64
I.S. Gulian, E.P. Bystritskaya, N.Yu. Otstavnykh, E.V. Khudchenko, E.V. Eliseeva, V.I. Apanasevich, M.P. Isaeva
1) Pacific State Medical University, Vladivostok, Russia; 2) Pacific Institute of Bioorganic Chemistry n.a. G.B. Elyakov, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia; 3) Far Eastern Federal University, Vladivostok, Russia; 4) Primorsky Regional Oncology Center, Vladivostok, Russia
Objective. Evaluation of the effects of GSTT1 and GSTM1 deletion polymorphisms on the risk of relapse in patients with hormone-positive breast cancer (BC) treated with tamoxifen.
Methods. The study examined blood samples from 102 women diagnosed with stage IIA–III BC, aged from 23 to 79 (average age – 48±13) years, who received adjuvant hormonal therapy (HT). Identification of deletion (null) genotypes of GSTM1 and GSTT1 was carried out using multiplex polymerase chain reaction followed by analysis of melting curves of the reaction products.
Results. A statistically significant association between the double GSTT1-GSTM1 deletions carriage and a reduced risk of developing BC relapse was revealed. According to estimates, in such patients the probability of relapse was 4.5 times lower compared with carriers of the “functional” GSTT1 and GSTM1 genotypes simultaneously (OR=0.219, 95% CI: 0.033–1.444, χ²=4.377; P=0.037). At the same time, the presence of a “null” GSTT1 variant reduced the relative risk (RR) of developing BC relapse by 1.9 times (RR=0.513, 95% CI: 0.211–1.246, χ²=2.909) compared with carriage of functionally active forms of GSTT1 (0/+, +/+). In this case, we can only talk about an emerging trend, because there was no statistically significant difference in values (P=0.089). According to estimates, the RR for the development of BC recurrence in the group of patients with a functionally inactive form of GSTM1 (0/0) was 1.2 times lower (RR=0.856, 95% CI: 0.541–1.356, χ²=0.442; P=0.507), however the resulting difference was not statistically significant.
Conclusion. A study of deletion polymorphisms of glutathione-S-transferase genes in women with BC revealed a significant association of the combination of “null” genotypes GSTM1 and GSTT1 with a reduced risk of disease relapse. Thus, carriage of these genotypes, leading to the absence of the corresponding glutathione-S-transferases, can be considered as a favorable predictive factor when conducting adjuvant HT with tamoxifen in patients with luminal BC type.
Methods. The study examined blood samples from 102 women diagnosed with stage IIA–III BC, aged from 23 to 79 (average age – 48±13) years, who received adjuvant hormonal therapy (HT). Identification of deletion (null) genotypes of GSTM1 and GSTT1 was carried out using multiplex polymerase chain reaction followed by analysis of melting curves of the reaction products.
Results. A statistically significant association between the double GSTT1-GSTM1 deletions carriage and a reduced risk of developing BC relapse was revealed. According to estimates, in such patients the probability of relapse was 4.5 times lower compared with carriers of the “functional” GSTT1 and GSTM1 genotypes simultaneously (OR=0.219, 95% CI: 0.033–1.444, χ²=4.377; P=0.037). At the same time, the presence of a “null” GSTT1 variant reduced the relative risk (RR) of developing BC relapse by 1.9 times (RR=0.513, 95% CI: 0.211–1.246, χ²=2.909) compared with carriage of functionally active forms of GSTT1 (0/+, +/+). In this case, we can only talk about an emerging trend, because there was no statistically significant difference in values (P=0.089). According to estimates, the RR for the development of BC recurrence in the group of patients with a functionally inactive form of GSTM1 (0/0) was 1.2 times lower (RR=0.856, 95% CI: 0.541–1.356, χ²=0.442; P=0.507), however the resulting difference was not statistically significant.
Conclusion. A study of deletion polymorphisms of glutathione-S-transferase genes in women with BC revealed a significant association of the combination of “null” genotypes GSTM1 and GSTT1 with a reduced risk of disease relapse. Thus, carriage of these genotypes, leading to the absence of the corresponding glutathione-S-transferases, can be considered as a favorable predictive factor when conducting adjuvant HT with tamoxifen in patients with luminal BC type.
About the Autors
Corresponding author: Isabella S. Gulian, Teaching Assistant at the Institute of Surgery, Pacific State Medical University; Oncologist, Medical Center, Far Eastern Federal University, Vladivostok, Russia; isabella.g@mail.ru
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