Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma

Cancer Med. 2015 Nov;4(11):1700-4. doi: 10.1002/cam4.500. Epub 2015 Aug 15.

Abstract

The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10(-5) ) although not genome-wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples.

Keywords: BARX1; FOXF1; FOXP1; esophageal adenocarcinoma; genetic association study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Adolescent
  • Adult
  • Alleles
  • Case-Control Studies
  • Esophageal Neoplasms / epidemiology
  • Esophageal Neoplasms / genetics*
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genetic Association Studies
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Repressor Proteins / genetics*
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • BARX1 protein, human
  • FOXF1 protein, human
  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • Repressor Proteins
  • Transcription Factors

Supplementary concepts

  • Adenocarcinoma Of Esophagus