Functional annotation of colon cancer risk SNPs

Nat Commun. 2014 Sep 30;5:5114. doi: 10.1038/ncomms6114.

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased risk for CRC. A molecular understanding of the functional consequences of this genetic variation has been complicated because each GWAS SNP is a surrogate for hundreds of other SNPs, most of which are located in non-coding regions. Here we use genomic and epigenomic information to test the hypothesis that the GWAS SNPs and/or correlated SNPs are in elements that regulate gene expression, and identify 23 promoters and 28 enhancers. Using gene expression data from normal and tumour cells, we identify 66 putative target genes of the risk-associated enhancers (10 of which were also identified by promoter SNPs). Employing CRISPR nucleases, we delete one risk-associated enhancer and identify genes showing altered expression. We suggest that similar studies be performed to characterize all CRC risk-associated enhancers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Colonic Neoplasms / genetics*
  • Enhancer Elements, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic