Candidate Causal Variants at the 8p12 Breast Cancer Risk Locus Regulate <i>DUSP4</i>.

ABSTRACT: Genome-wide association studies have revealed a locus at 8p12 that is associated with breast cancer risk. Fine-mapping of this locus identified 16 candidate causal variants (CCVs). However, as these variants are intergenic, their function is unclear. To map chromatin looping from this risk locus to a previously identified candidate target gene, DUSP4, we performed chromatin conformation capture analyses in normal and tumoural breast cell lines. We identified putative regulatory elements, containing CCVs, which looped to the DUSP4 promoter region. Using reporter gene assays, we found that the risk allele of CCV rs7461885 reduced the activity of a DUSP4 enhancer element, consistent with the function of DUSP4 as a tumour suppressor gene. Furthermore, the risk allel

SUBMITTER: Glubb DM 

PROVIDER: S-EPMC7016765 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature