The role of GSTP1 and MTHFR gene polymorphic markers in the decreased response to doxorubicin therapy of breast cancer patients

  • S. S. Lukina Institute of General Pathology and Pathophysiology, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  • T. M. Zavarykina N.M. Emanuel Institute for Biochemical Physics, Moscow, Russia
  • N. A. Ivanova Institute of General Pathology and Pathophysiology, Moscow, Russia
  • I. V. Pronina Institute of General Pathology and Pathophysiology, Moscow, Russia
  • T. P. Kazubskaya N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
  • M. P. Kruglova I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  • D. A. Ryabchikov N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
  • V. I. Loginov Institute of General Pathology and Pathophysiology, Moscow, Russia http://orcid.org/0000-0003-2668-8096
  • A. M. Burdennyy Institute of General Pathology and Pathophysiology, Moscow, Russia; N.M. Emanuel Institute for Biochemical Physics, Moscow, Russia http://orcid.org/0000-0002-9398-8075
DOI: https://doi.org/10.25557/2310-0435.2020.03.53-60
Keywords: breast cancer, GSTP1 gene, MTHFR gene, doxorubicin, risk of development, sensitivity, survival

Abstract

Background. Breast cancer (BC) is a multifactorial disease. Different factors contribute to the BC pathogenesis, including genetic factors, such as single-nucleotide variations in genes of xenobiotic biotransformation and one-carbon metabolism. Specifically, changes in GSTP1 and MTHFR genes influence the risk of BC and may result in a decreased response of the tumor to anthracycline drugs, such as doxorubicin.
Aim. The aim of this study was to evaluate the effect of polymorphic markers, rs1695 of the GSTP1 gene and rs1801133 and rs1801131 of the MTHFR gene, on the risk of BC and sensitivity to the doxorubicin therapy.
Methods. The study included 239 BC patients from Moscow and the Moscow Region with established clinical pathomorphological features of the tumor, including the immune histological status. The population control group consisted of age-matched women without an oncological disease (n = 200). Genotypes of rs1695, rs1801133, and rs1801131 polymorphic markers were determined by analysis of DNA melting curves with real-time PCR performed on a Real-time CFX96 Touch amplifier (Bio-Rad, USA) with a qPCRmix-HS ready-to-use PCR kit (Eurogen, Russia).
Results. The study showed statistically significant associations of the GSTP1 gene rs1695 polymorphic marker and the MTHFR gene rs1801133 polymorphic marker with the risk of BC (OR = 1.15, CI95% = 1.14-2.00; p = 0.0114 and OR = 1.57, CI95% = 1.19-2.08; p = 0.0023, respectively). The study of polymorphic marker association with response to the doxorubicin chemotherapy showed that in the group of patients with a poor response to chemotherapy, frequencies of the Val allele in the GSTP1 gene rs1695 polymorphic marker and the C allele in the MTHFR gene rs1801133 polymorphic marker were significantly increased. Also, the MTHFR gene rs1801133 polymorphic marker (p = 0.0397) was significantly associated with survival of BC patients.
Conclusion. The results of this study supplemented information about causes for resistance to doxorubicin and will allow isolating groups at risk with a negative response to the doxorubicin chemotherapy.

Published
2020-09-03
How to Cite
Lukina, S. S., Zavarykina, T. M., Ivanova, N. A., Pronina, I. V., Kazubskaya, T. P., Kruglova, M. P., Ryabchikov, D. A., Loginov, V. I., & Burdennyy, A. M. (2020). The role of GSTP1 and MTHFR gene polymorphic markers in the decreased response to doxorubicin therapy of breast cancer patients. Patogenez (Pathogenesis), 18(3), 53-60. https://doi.org/10.25557/2310-0435.2020.03.53-60
Issue
Vol. 18 No. 3 (2020): Pathogenesis
Section
Clinical researches