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

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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.

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Authors and Affiliations

  1. Department of Experimental Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5, Kooperativny Street, 634050, Tomsk, Russian Federation

    Matvey M. Tsyganov, Marina K. Ibragimova, Irina V. Deryusheva, Nadezhda V. Cherdyntseva & Nikolai V. Litviakov

  2. Department of General Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5, Kooperativny Street, 634050, Tomsk, Russian Federation

    Polina V. Kazantseva & Elena M. Slonimskaya

  3. Laboratory of Population Genetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Nabereznaya Ushaiky Str., 634050, Tomsk, Russian Federation

    Maxim B. Freidin

Authors
  1. Matvey M. Tsyganov
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  2. Maxim B. Freidin
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  3. Marina K. Ibragimova
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  4. Irina V. Deryusheva
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  5. Polina V. Kazantseva
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  6. Elena M. Slonimskaya
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  8. Nikolai V. Litviakov
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Corresponding author

Correspondence to Matvey M. Tsyganov.

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Conflict of interest

All authors declared that they have no potential conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

The study is funded by the Russian Science Foundation No. 17-15-01203 “Metastatic breast tumor clones”.

Informed consent

Informed consent was obtained from all individual participants included in the study. The experiments comply with the current laws of the country.

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Tsyganov, M.M., Freidin, M.B., Ibragimova, M.K. et al. Genetic variability in the regulation of the expression cluster of MDR genes in patients with breast cancer. Cancer Chemother Pharmacol 80, 251–260 (2017). https://doi.org/10.1007/s00280-017-3354-1

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  • DOI: https://doi.org/10.1007/s00280-017-3354-1

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