Features of associations of SHBG-related genes with breast cancer in women, depending on the presence of hereditary burden and mutations in the BRCA1/CHEK2 genes

Background: One of the most common diseases of the female population is breast cancer (BC), which is a hormone-dependent pathology and has a significant hereditary component. Candidate genes that determine the concentrations of the protein transporting sex hormones (SHBG) in the body may be promising genetic risk factors for the development of BC. The aim of the study: To evaluate the features of associations of SHBG-related genes with BC in women, depending on the presence/absence of hereditary burden and mutations in the BRCA1/CHEK2 genes. Materials and methods: A sample of BC patients (n=358) depending on the presence/absence of a burdened family history (n=68 and n=290, respectively), as well as depending on the presence/absence of mutations in the BRCA1/CHEK2 genes (n=26 and n=332, respectively), was divided into appropriate subgroups for comparative genetic analysis with the control group (n=1140). The paper considers nine polymorphisms of SHBG-significant genes – PRMT6 (rs17496332), GCKR (rs780093), PPP1R21 (rs10454142), BAIAP2L1 (rs3779195), ZBTB10 (rs440837), JMJD1C (rs7910927), SLCO1B1 (rs4149056), NR2F2 (rs8023580), SHBG (rs12150660). Associations were studied using logistic regression. Results: Significant differences were found in the involvement of SNP SHBG-related genes in the predisposition to BC, depending on the presence/absence of a burdened family history and mutations in the BRCA1/CHEK2 genes in patients. SNP rs10454142 PPP1R21 is associated with BC in women who do not have a burdened family history of BC (risk allele – C; additive model OR=1.32 95%CI=1.03-1.70 p=0.027 pperm=0.027), and in women who had no mutations in the BRCA1/CHEK2 genes (risk allele – C; additive model OR=1.34 95%CI=1.05-1.70 p=0.017 pperm=0.017; recessive model OR=1.74 95%CI=1.05-2.86 p=0.030 pperm=0.034). At the same time, among women who have BC-burdened heredity or mutations in the BRCA1/CHEK2 genes, polymorphic variants of SHBGrelated genes do not have an independent effect on the risk of developing the disease. Conclusion: rs10454142 PPP1R21 polymorphism is a risk factor for breast cancer in women without burdened heredity and in women without mutations in the BRCA1/CHEK2 genes.