Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia
In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 c...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/4/2182 |
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| author | Irina Ponomarenko Konstantin Pasenov Maria Churnosova Inna Sorokina Inna Aristova Vladimir Churnosov Marina Ponomarenko Evgeny Reshetnikov Mikhail Churnosov |
| author_facet | Irina Ponomarenko Konstantin Pasenov Maria Churnosova Inna Sorokina Inna Aristova Vladimir Churnosov Marina Ponomarenko Evgeny Reshetnikov Mikhail Churnosov |
| author_sort | Irina Ponomarenko |
| collection | DOAJ |
| description | In our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 <i>GCKR</i>, rs17496332 <i>PRMT6</i>, rs3779195 <i>BAIAP2L1</i>, rs10454142 <i>PPP1R21</i>, rs7910927 <i>JMJD1C</i>, rs4149056 <i>SLCO1B1</i>, rs440837 <i>ZBTB10</i>, rs12150660 <i>SHBG</i>, and rs8023580 <i>NR2F2</i> have been genotyped. BC risk effects of allelic and non-allelic SHBG-linked gene SNPs interactions were detected by regression analysis. The risk genetic factor for BC developing is an SHBG-lowering allele variant C rs10454142 <i>PPP1R21</i> ([additive genetic model] OR = 1.31; 95%CI = 1.08–1.65; p<sub>perm</sub> = 0.024; power = 85.26%), which determines 0.32% of the cancer variance. Eight of the nine studied SHBG-related SNPs have been involved in cancer susceptibility as part of nine different non-allelic gene interaction models, the greatest contribution to which is made by rs10454142 <i>PPP1R21</i> (included in all nine models, 100%) and four more SNPs—rs7910927 <i>JMJD1C</i> (five models, 55.56%), rs17496332 <i>PRMT6</i> (four models, 44.44%), rs780093 <i>GCKR</i> (four models, 44.44%), and rs440837 <i>ZBTB10</i> (four models, 44.44%). For SHBG-related loci, pronounced functionality in the organism (including breast, liver, fibroblasts, etc.) was predicted in silico, having a direct relationship through many pathways with cancer pathophysiology. In conclusion, our results demonstrated the involvement of SHBG-correlated genes polymorphisms in BC risk in Caucasian women in Russia. |
| first_indexed | 2024-03-07T22:29:13Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-07T22:29:13Z |
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| spelling | doaj.art-f3363b2d00144a7ba4a13b5d3f6b53202024-02-23T15:20:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01254218210.3390/ijms25042182Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of RussiaIrina Ponomarenko0Konstantin Pasenov1Maria Churnosova2Inna Sorokina3Inna Aristova4Vladimir Churnosov5Marina Ponomarenko6Evgeny Reshetnikov7Mikhail Churnosov8Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaIn our work, the associations of GWAS (genome-wide associative studies) impact for sex-hormone-binding globulin (SHBG)-level SNPs with the risk of breast cancer (BC) in the cohort of Caucasian women of Russia were assessed. The work was performed on a sample of 1498 women (358 BC patients and 1140 control (non BC) subjects). SHBG correlated in previously GWAS nine polymorphisms such as rs780093 <i>GCKR</i>, rs17496332 <i>PRMT6</i>, rs3779195 <i>BAIAP2L1</i>, rs10454142 <i>PPP1R21</i>, rs7910927 <i>JMJD1C</i>, rs4149056 <i>SLCO1B1</i>, rs440837 <i>ZBTB10</i>, rs12150660 <i>SHBG</i>, and rs8023580 <i>NR2F2</i> have been genotyped. BC risk effects of allelic and non-allelic SHBG-linked gene SNPs interactions were detected by regression analysis. The risk genetic factor for BC developing is an SHBG-lowering allele variant C rs10454142 <i>PPP1R21</i> ([additive genetic model] OR = 1.31; 95%CI = 1.08–1.65; p<sub>perm</sub> = 0.024; power = 85.26%), which determines 0.32% of the cancer variance. Eight of the nine studied SHBG-related SNPs have been involved in cancer susceptibility as part of nine different non-allelic gene interaction models, the greatest contribution to which is made by rs10454142 <i>PPP1R21</i> (included in all nine models, 100%) and four more SNPs—rs7910927 <i>JMJD1C</i> (five models, 55.56%), rs17496332 <i>PRMT6</i> (four models, 44.44%), rs780093 <i>GCKR</i> (four models, 44.44%), and rs440837 <i>ZBTB10</i> (four models, 44.44%). For SHBG-related loci, pronounced functionality in the organism (including breast, liver, fibroblasts, etc.) was predicted in silico, having a direct relationship through many pathways with cancer pathophysiology. In conclusion, our results demonstrated the involvement of SHBG-correlated genes polymorphisms in BC risk in Caucasian women in Russia.https://www.mdpi.com/1422-0067/25/4/2182SHBGbreast cancerSNPassociation |
| spellingShingle | Irina Ponomarenko Konstantin Pasenov Maria Churnosova Inna Sorokina Inna Aristova Vladimir Churnosov Marina Ponomarenko Evgeny Reshetnikov Mikhail Churnosov Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia International Journal of Molecular Sciences SHBG breast cancer SNP association |
| title | Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia |
| title_full | Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia |
| title_fullStr | Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia |
| title_full_unstemmed | Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia |
| title_short | Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia |
| title_sort | sex hormone binding globulin gene polymorphisms and breast cancer risk in caucasian women of russia |
| topic | SHBG breast cancer SNP association |
| url | https://www.mdpi.com/1422-0067/25/4/2182 |
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