In breast cancer, germline SNPs at 11q13 in the vicinity of CCND1 have puzzled researchers for decades. Cyclin D1 (CCND1) is key to cancer development: over-expression of CCND1 has been found in numerous cancers, whilst repression of CCND1 impairs homologous recombination-mediated DNA repair, making cells more sensitive to damaging agents.|
From GWAS, rs614367 is one of the SNPs most associated with ER+ (oestrogen-positive) breast cancer (p = 10− 39) . The only problem with rs614367 is that it is located in a large intergenic region, upstream of CCND1 - its function and how it alters CCND1 expression remains unknown. A separate study then found more intergenic SNPs at 11q13 in linkage disequilibrium with the original SNP, rs614367. These newly-identified SNPs are located within known enhancers and silencers of CCND1: PRE1 and PRE2 (putative regulatory elements 1 and 2) . Their role is thought to be in modulating the binding of the ELK4 and GATA3 transcription factors, most likely modifying transcription of CCND1.
Conclusion: The exact mechanism is still yet to be understood.