Polymorphic locus rs8023580 NR2F2-AS1 is associated with breast cancer risk in residents of Central Russia

Breast cancer (BC) is the most common hormone-dependent genetically determined cancer among women. The level of “active” sex hormones in the body, the connection of which with breast cancer is beyond doubt, is determined by the content of the protein transporting sex hormones (SHBG).Aim: To study associations of polymorphic loci linked with the level of SHBG at the full-genomic level of significance with the risk of developing breast cancer.Material and Methods. The work was carried out on a sample of 1,498 women, 358 of whom were BC patients, the control was 1140 individuals. Genotyping of four single nucleotide polymorphic loci (SNP) associated with the level of SHBG was performed according to previously performed genome-wide studies (GWAS): rs7910927 JMJD1C, rs4149056 SLCO1B1, rs8023580 NR2F2-AS1, rs12150660 SHBG. The method of logistic regression was used to search for associations.Results and Discussion. SNP rs8023580 of the NR2F2-AS1 gene is associated with the risk of BC developing. The presence of the CC genotype rs8023580 NR2F2-AS1in a woman has a protective value in the formation of the disease (CCvsTC+TT [recessive model]; OR = 0.58; 95%CI = 0.35-0.96; p = 0.033; pperm = 0.042). SNP rs8023580 NR2F2-AS1 is functionally significant in the liver: it is localized in the enhancer region, affects the level of methylation of the cg01739960 (hg38) genome region, affects the expression of the RP11-327J17.2 gene, determines the interaction of DNA with six transcription factors (Fo xd1,Foxl1,Foxq1,Mef2,PLZF,STAT), which are located in the cis-regulatory region of RNA polymerase II, specific for the DNA binding sequence, and determine the activity of DNA-binding transcription factors specific for RNA polymerase II, are involved in the processes of cellular differentiation and tissue development.Conclusion. The SHBG-enhancing CC genotype rs8023580 of the NR2F2-AS1 gene is a protective factor in the development of BC.