The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer

Abstract

Matthew Freedman and colleagues show that a region on 8q24 associated with colorectal cancer risk functions as an enhancer and undergoes long-range interactions with MYC. They further show that alleles at the risk-associated SNP bind differentially to TCF7L2, a transcription factor in the Wnt pathway. An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that the region harboring this variant is a transcriptional enhancer, that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2) and that the risk region physically interacts with the MYC proto-oncogene. These data provide strong support for a biological mechanism underlying this non-protein-coding risk variant.