Features of gene polymorphism associations linked with sex hormone binding globulin level and breast cancer of various molecular biological subtypes

Aim : to identify specific associations between genes polymorphism associated with sex hormone-binding globulin (SHBG) level and breast cancer (BC) of various molecular biological subtypes. Materials and Methods . The retrospective comparative study was conducted using specimens collected from 261 patients with BC of two molecular biological subtypes – luminal A/B (n = 153) and triple negative (n = 108) as well as 1140 women in control group. All study participants (n = 1401) underwent a molecular genetic study of four single nucleotide polymorphism (SNP) loci, which showed a relationship with circulating SHBG level in previously conducted genome-wide association study (GWAS): rs12150660 SHBG , rs10454142 PPP1R21 , rs780093 GCKR , rs17496332 PRMT6 . Results . The analysis revealed an association between SHBG SNP candidate genes and a BC risk in patients with luminal A/B subtypes and lacked significant associations between the loci assessed and triple negative BC subtype. CC female genotype of rs10454142 PPP1R21 increased a risk of luminal A/B subtypes BC by more than 2-fold (recessive model [CC vs. TC+TT]; odds ratio = 2.07; 95 % confidence interval = 1.14–3.77; p = 0.017; p perm = 0.018). This SNP is localized in functionally "significant" regions of the genome (enhancers/active enhancers, promoters/active promoters) and affects methylation level in several hepatocyte DNA sites [cg15846641 (chr2:48541264)].