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Gene-to-gene interactions and the association of TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 with breast cancer in Kyrgyz females



At present, little is known about the genetic background of breast cancer (BC) in Kyrgyz. Therefore, the aim of this study was to assess gene-to-gene interactions and the contribution of p.Arg72Pro (TP53 gene), p.Gln399Arg (XRCC1 gene), p.Arg194Trp (XRCC1 gene), g.4682G > A (TNFα gene), p.Val353Ala (HMMR gene), c.14 + 309 T > G (MDM2 gene) and g.38444 T > G (PALB2 gene) polymorphic loci in breast cancer (BC) risk in females of Kyrgyz ethnicity.


The case–control study comprised 103 females with histologically verified BC and 102 controls with no cancer. We used polymerase chain reaction-based restriction fragment length polymorphism to genotype polymorphic loci.


Gln/Arg heterozygous variant of XRCC1 gene’s p.Gln399Arg locus, as well as combined carriage of Arg/Gln//Arg/Pro of XRCC1/TP53; Arg/Gln//T/T of XRCC1/MDM2; Arg/Gln//G/G and Arg/Gln//G/A of XRCC1/TNFα, Arg/Gln//T/T of XRCC1/PALB2; Arg/Gln//Arg/Arg and Arg/Gln//Arg/Trp for p.Gln399Arg and p.Arg194Trp polymorphic loci of XRCC1 were associated with BC in Kyrgyz females.


TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 genes’ polymorphic site combinations appear to be candidate markers of genetic predisposition to BC in Kyrgyz population and prompt targeted personalized care.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.


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We thank all patients for their participation in this study.


This study was supported by the Ministry of Education and Science of Kyrgyz Republic, State Register #0005818, dated February 2, 2017.

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Corresponding author

Correspondence to J. T. Isakova.

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The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (The Ethics Committee of Institute of Molecular Biology and Medicine, No. IMBM/IEC/04-13/987, July 07, 2017) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Isakova, J.T., Vinnikov, D., Kipen, V.N. et al. Gene-to-gene interactions and the association of TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 with breast cancer in Kyrgyz females. Breast Cancer 27, 938–946 (2020).

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  • Breast cancer
  • Polymorphism
  • Genes
  • TP53
  • XRCC1
  • TNFα
  • HMMR
  • MDM2
  • PALB2
  • Kyrgyz population