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Polymorphism rs1940475 of the MMP8 gene is a protective factor of severe breast cancer

https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.334

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Abstract

Aim: to study the associations of polymorphism of the MMP2, MMP8, MMP9 genes with severe breast cancer (BC).

Materials and Methods. Retrospective сomparative study was conducted on a sample of 345 patients with BC: 254 patients had I–II stages of the disease and 91 had III–-IV stages. Genotyping of four single nucleotide polymorphisms MMP2 (C>T rs243865), MMP8 (C>T rs1940475), ММР9 (C>T rs3918242) was performed. A comparative analysis of the genetic characteristics of patients with stages I-II and III-IV of the disease was performed.

Results. The allele variant T rs1940475 (C>T) of the MMP8 gene is found among patients with BC of stages I–II (0.512) 1.2 times more often in comparison with patients with stages III–IV of the disease (0.428; pperm = 0.05). According to allelic (OR = 0.71; 95 % CI = 0.51–1.00; pperm = 0.05) and additive (OR = 0.69; 95 % CI = 0.48–0.99; pperm = 0.05) genetic models, the allele T rs1940475 (C>T) of the MMP8 gene has protective values for the development of stage III–IV of BC. The polymorphic locus rs1940475 (C>T) determines the amino acid substitution in the MMP8 protein (p.K87E) and the binding of DNA to transcription factors NF-AT1, MYC and CIZ, is associated with the expression of the genes MMP27 and RP11-817J15.3, is an enhancer regulatory site in primary epithelial cells of the breast. Single nucleotide polymorphism MMP2 (C>T rs243865), ММР9 (C>T rs3918242) is not associated with severe BC (stages III–IV).

Conclusion. The single nucleotide polymorphism rs1940475 of the MMP8 gene is a protective factor in the severe course of BC.

About the Authors

N. V. Pavlova
Belgorod Regional Oncological Dispensary
Russian Federation

Nadezhda V. Pavlova – MD, Head of the Polyclinic Department

1 Kuibyshev Str., Belgorod 308010



I. V. Ponomarenko
Belgorod State National Research University
Russian Federation

Irina V. Ponomarenko – MD, Dr Sci Med, Professor, Department of Biomedical Disciplines

85 Pobedy Str., Belgorod 308007



M. I. Churnosov
Belgorod State National Research University
Russian Federation

Mikhail I. Churnosov – MD, Dr Sci Med, Professor, Head of the Department of Biomedical Disciplines

85 Pobedy Str., Belgorod 308007



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Review

For citations:


Pavlova N.V., Ponomarenko I.V., Churnosov M.I. Polymorphism rs1940475 of the MMP8 gene is a protective factor of severe breast cancer. Obstetrics, Gynecology and Reproduction. 0;. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.334

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