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Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia
We conducted this study to explore the association between matrix metalloproteinase (MMP) gene polymorphisms and breast cancer (BC) risk in the Caucasian women of Russia. In total, 358 affected (BC) and 746 unaffected (cancer-free) women were included in this case-control retrospective study. From B...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604098/ https://www.ncbi.nlm.nih.gov/pubmed/36293492 http://dx.doi.org/10.3390/ijms232012638 |
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author | Pavlova, Nadezhda Demin, Sergey Churnosov, Mikhail Reshetnikov, Evgeny Aristova, Inna Churnosova, Maria Ponomarenko, Irina |
author_facet | Pavlova, Nadezhda Demin, Sergey Churnosov, Mikhail Reshetnikov, Evgeny Aristova, Inna Churnosova, Maria Ponomarenko, Irina |
author_sort | Pavlova, Nadezhda |
collection | PubMed |
description | We conducted this study to explore the association between matrix metalloproteinase (MMP) gene polymorphisms and breast cancer (BC) risk in the Caucasian women of Russia. In total, 358 affected (BC) and 746 unaffected (cancer-free) women were included in this case-control retrospective study. From BC-related genes in previous studies, ten single nucleotide polymorphisms (SNPs) in five MMP genes (MMP1, 2, 3, 8, 9) were genotyped. The BC risk was calculated by logistic regression (to evaluate the SNPs’ independent effects) and model-based multifactor dimensionality reduction (MB-MDR) (to identify SNP–SNP interactions) methods. The allelic variants’ distribution of c.836 A > G (rs17576) and c. 1721 C > G (rs2250889) MMP9 was significantly different between BC and cancer-free women: for G minor alleles, these SNPs manifested disorder protective effects (OR 0.82 and OR 0.67–0.71, respectively, p(perm) ≤ 0.035). Eleven haplotypes of six SNPs MMP9 were involved in BC risk (nine haplotypes) and protective (two haplotypes) effects. All 10 SNPs of the MMP genes examined were associated with BC within the 13 SNP–SNP interaction simulated models, with a pivotal role of the two-locus (rs17577 × rs3918242) MMP9 epistatic interaction (defined as 1.81% BC entropy within more than 60% of the genetic models). Under in silico bioinformatics, BC susceptibility MMP polymorphic loci are located in functionally active genome regions and impact genes expression and splicing “regulators” in the mammary gland. The biological pathways of BC MMP candidate genes are mainly realized due to metalloendopeptidase activity and extracellular matrix organization (structure, disassembly, metabolic process, etc.). In conclusion, our data show that MMP gene polymorphisms are related to BC susceptibility in the Caucasian women of Russia. |
format | Online Article Text |
id | pubmed-9604098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96040982022-10-27 Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia Pavlova, Nadezhda Demin, Sergey Churnosov, Mikhail Reshetnikov, Evgeny Aristova, Inna Churnosova, Maria Ponomarenko, Irina Int J Mol Sci Article We conducted this study to explore the association between matrix metalloproteinase (MMP) gene polymorphisms and breast cancer (BC) risk in the Caucasian women of Russia. In total, 358 affected (BC) and 746 unaffected (cancer-free) women were included in this case-control retrospective study. From BC-related genes in previous studies, ten single nucleotide polymorphisms (SNPs) in five MMP genes (MMP1, 2, 3, 8, 9) were genotyped. The BC risk was calculated by logistic regression (to evaluate the SNPs’ independent effects) and model-based multifactor dimensionality reduction (MB-MDR) (to identify SNP–SNP interactions) methods. The allelic variants’ distribution of c.836 A > G (rs17576) and c. 1721 C > G (rs2250889) MMP9 was significantly different between BC and cancer-free women: for G minor alleles, these SNPs manifested disorder protective effects (OR 0.82 and OR 0.67–0.71, respectively, p(perm) ≤ 0.035). Eleven haplotypes of six SNPs MMP9 were involved in BC risk (nine haplotypes) and protective (two haplotypes) effects. All 10 SNPs of the MMP genes examined were associated with BC within the 13 SNP–SNP interaction simulated models, with a pivotal role of the two-locus (rs17577 × rs3918242) MMP9 epistatic interaction (defined as 1.81% BC entropy within more than 60% of the genetic models). Under in silico bioinformatics, BC susceptibility MMP polymorphic loci are located in functionally active genome regions and impact genes expression and splicing “regulators” in the mammary gland. The biological pathways of BC MMP candidate genes are mainly realized due to metalloendopeptidase activity and extracellular matrix organization (structure, disassembly, metabolic process, etc.). In conclusion, our data show that MMP gene polymorphisms are related to BC susceptibility in the Caucasian women of Russia. MDPI 2022-10-20 /pmc/articles/PMC9604098/ /pubmed/36293492 http://dx.doi.org/10.3390/ijms232012638 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pavlova, Nadezhda Demin, Sergey Churnosov, Mikhail Reshetnikov, Evgeny Aristova, Inna Churnosova, Maria Ponomarenko, Irina Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia |
title | Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia |
title_full | Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia |
title_fullStr | Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia |
title_full_unstemmed | Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia |
title_short | Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia |
title_sort | matrix metalloproteinase gene polymorphisms are associated with breast cancer in the caucasian women of russia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604098/ https://www.ncbi.nlm.nih.gov/pubmed/36293492 http://dx.doi.org/10.3390/ijms232012638 |
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