An interplay between genes SLCO1B1, NR2F2, JMJD1C and obesity in developing breast cancer

Aim: to evaluate a role of polymorphic variants rs4149056 SLCO1B1, rs8023580 NR2R2 and rs7910927 JMJD1C in developing obesity-related female breast cancer (BC).Materials and Methods. A retrospective comparative study was performed on a sample of 1,498 women (358 BC patients and 1,140 control subjects) stratified into 2 groups based on verified obesity: obese (119 BC patients and 253 control subjects) and non-obese (239 BC patients and 887 control subjects). Genotyping of three single nucleotide polymorphisms (SNP) – rs7910927 JMJD1C, rs8023580 NR2F2, rs4149056 SLCO1B1 was performed to be further analyzed separately in each group of obese and non-obese women for associations of such loci and interplay with breast cancer.Results. Polymorphisms rs8023580 NR2F2, rs4149056 SLCO1B1 and rs7910927 JMJD1C are not independently associated with BC in obese and non-obese women, whereas their interlocus interactions are BC-significant in each of the examined groups (pperm = 0.047 and pperm = 0.0012, respectively). Among obese women, the combination of TC-TT-GG genotypes (for rs8023580–rs4149056–rs7910927) is associated with a low risk of developing BC (β = –2.45), whereas the combination of TC-TC-GG genotypes is associated with increased BC risk (β=1.42). In non-obese women, a combination of the TC-TT-GT genotypes (β = –0.47) has a protective effect on the BC occurrence, and the risk effect is coupled to TC-TC-GT (β = 0.91) and TC-CC-GT (β = 1.45). The appearance of allele C rs4149056 in female genotype and its increased "concentration" results in higher BC risk.Conclusion. The allele variant C rs4149056 in the interlocus interactions between the SLCO1B1, NR2F2 and JMJD1C genes is a "universal" factor that elevates BC risk in both obese and non-obese women. The genotype GG rs7910927 is BC-significant in interlocus interactions in obese women, whereas in non-obese women it is coupled to the genotype GT rs7910927.