8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC.

The 8q24 gene desert contains risk loci for multiple epithelial cancers, including colon, breast, and prostate. Recent evidence suggests these risk loci contain enhancers. In this study, data are presented showing that each risk locus bears epigenetic marks consistent with enhancer elements and forms a long-range chromatin loop with the MYC proto-oncogene located several hundred kilobases telomeric and that these interactions are tissue-specific.

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

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.

Evaluation of the 8q24 prostate cancer risk locus and MYC expression.

Polymorphisms at 8q24 are robustly associated with prostate cancer risk. The risk variants are located in nonprotein coding regions and their mechanism has not been fully elucidated. To further dissect the function of this locus, we tested two hypotheses: (a) unannotated microRNAs (miRNA) are transcribed in the region, and (b) this region is a cis-acting enhancer.

Evaluation of 8q24 and 17q risk loci and prostate cancer mortality.

Purpose: Variants at chromosomal loci 8q24 and 17q are established risk factors for prostate cancer. Many studies have confirmed the findings for risk, but few have examined aggressiveness and other clinical variables in detail. Additionally, Gleason score is typically used as a surrogate for the primary end point of prostate cancer mortality.