A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus

Nat Genet. 2013 Dec;45(12):1487-93. doi: 10.1038/ng.2796. Epub 2013 Oct 13.

Abstract

Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Barrett Esophagus / epidemiology
  • Barrett Esophagus / genetics*
  • Barrett Esophagus / pathology
  • Case-Control Studies
  • Esophageal Neoplasms / epidemiology
  • Esophageal Neoplasms / genetics*
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease* / genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Grant support