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DOI: 10.18413/2658-6533-2022-8-2-0-4

The role of highly penetrant mutations in BRCA1 and CHEK2 genes in the pattern of associations of matrix metalloproteinase gene polymorphisms with breast cancer

Background: Breast cancer (BC) is a malignant breast tumor, which occupies a leading place both in the structure of oncological diseases in women and among the causes of female mortality from malignant neoplasms. The role of genetic factors in the formation of breast cancer is beyond doubt. The aim of the study: To study the role of highly penetrant mutations in BRCA1 and CHEK2 genes in the pattern of associations of matrix metalloproteinase genes (MMP) polymorphism with BC. Materials and methods: To solve the research goal, the following three samples were formed: 26 BC patients with highly penetrant mutations in the BRCA1 (c.5266dup (5382insC), c.68_69del (185delAG), 2080delA) and CHEK2 (I157T)) genes, 332 BC patients without germinal mutations in the BRCA1 (c.5266dup (5382insC), c.68_69del (185delAG), 2080delA, 4153delA), BRCA2 (6174delT) and CHEK2 (I157T) genes and 746 women of the control group. Ten polymorphisms of five matrix metalloproteinase genes (MMP1, MMP2, MMP3, MMP8 and MMP9) were studied. The analysis of associations was carried out by the method of logistic regression. Results: The TT rs1940475 MMP8 genotype in BC patients with highly penetrant mutations in the BRCA1 and CHEK2 genes (3.84%) is 6-7 times less common in comparison with both patients without these mutations (22.80% pperm=0.04) and control group individuals (26.18% ORcov=0.11 95%CIcov 0.01-0.81 pperm=0.03). In BC patients who do not have highly penetrant mutations in the BRCA1 and CHEK2 genes, MMP9 gene polymorphisms are associated with the disease: rs17576 (ORcov=0.81 pperm=0.03), rs2250889 (ORcov=0.61-0.66 pperm=0.03), rs3787268 (ORcov=2.03 pperm=0.04) and nine different haplotypes of the six studied MMP9 loci (pperm<0.05). Conclusion: The rs1940475 MMP8 polymorphic locus is associated with the risk of developing BC in women with highly penetrant mutations in the BRCA1 and CHEK2 genes, and polymorphisms of the MMP9 gene are associated with the disease in women without these mutations.

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