From: Gene editing in the context of an increasingly complex genome
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.