Common genetic variation in ETV6 is associated with colorectal cancer susceptibility

Nat Commun. 2016 May 5:7:11478. doi: 10.1038/ncomms11478.

Abstract

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for colorectal cancer, but much of heritability remains unexplained. To identify additional susceptibility loci for colorectal cancer, here we perform a GWAS in 1,023 cases and 1,306 controls and replicate the findings in seven independent samples from China, comprising 5,317 cases and 6,887 controls. We find a variant at 12p13.2 associated with colorectal cancer risk (rs2238126 in ETV6, P=2.67 × 10(-10)). We replicate this association in an additional 1,046 cases and 1,076 controls of European ancestry (P=0.034). The G allele of rs2238126 confers earlier age at onset of colorectal cancer (P=1.98 × 10(-6)) and reduces the binding affinity of transcriptional enhancer MAX. The mRNA level of ETV6 is significantly lower in colorectal tumours than in paired normal tissues. Our findings highlight the potential importance of genetic variation in ETV6 conferring susceptibility to colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / genetics
  • Cell Line, Tumor
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics*
  • ETS Translocation Variant 6 Protein
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Genotype
  • HCT116 Cells
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins c-ets / genetics*
  • Repressor Proteins / genetics*
  • Risk Factors
  • White People / genetics

Substances

  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins

Associated data

  • Dryad/10.5061/dryad.7dj7t