Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 2, pp 251–260 | Cite as

Genetic variability in the regulation of the expression cluster of MDR genes in patients with breast cancer

  • Matvey M. Tsyganov
  • Maxim B. Freidin
  • Marina K. Ibragimova
  • Irina V. Deryusheva
  • Polina V. Kazantseva
  • Elena M. Slonimskaya
  • Nadezhda V. Cherdyntseva
  • Nikolai V. Litviakov
Original Article

Abstract

Purpose

We aimed to investigate the association between the polymorphism and expression patterns of multiple drug resistance genes (MDR) in breast cancer (BC).

Materials and methods

The MDR gene expression levels were measured in tumor tissues of 106 breast cancer patients using quantitative real-time PCR. Affymetrix CytoScan™ HD Array chips were used to assess genotypes. Pairwise correlation analysis for ABCB1, ABCC1, ABCC2 and ABCG2 gene expression levels was carried out to reveal co-expression clusters. Associations between SNPs of MDR genes and their preoperative expression levels were assessed using analysis of covariance adjusting for covariates.

Results

The SNPs associated with the expression of the ABCB1, ABCC1, ABCC2 and ABCG2 genes before NAC were detected. In addition, 21 SNPs associated with the expression of four ABC-transporter genes and involved in the expression regulation were identified. Validation in an independent sample confirmed the association between the MDR cluster genes and 11 SNPs.

Conclusions

Four MDR genes: ABCB1, ABCC1, ABCC2 and ABCG2 were shown to form the functional expression cluster in breast tumor. Further studies are required to discover precise mechanisms of the cluster regulation, thereby providing new approaches and targets to combat the development of the MDR phenotype during chemotherapy.

Keywords

Breast cancer Single nucleotide polymorphism Multiple drug resistance Neoadjuvant chemotherapy Gene expression 

Supplementary material

280_2017_3354_MOESM1_ESM.docx (28 kb)
Supplementary material 1 (DOCX 28 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Matvey M. Tsyganov
    • 1
  • Maxim B. Freidin
    • 3
  • Marina K. Ibragimova
    • 1
  • Irina V. Deryusheva
    • 1
  • Polina V. Kazantseva
    • 2
  • Elena M. Slonimskaya
    • 2
  • Nadezhda V. Cherdyntseva
    • 1
  • Nikolai V. Litviakov
    • 1
  1. 1.Department of Experimental Oncology, Cancer Research Institute, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation
  2. 2.Department of General Oncology, Cancer Research Institute, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation
  3. 3.Laboratory of Population Genetics, Research Institute of Medical Genetics, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation

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