Common Genetic Variants Predisposing to Barrett's Esophagus Identified
“Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis,” noted Janusz Jankowski, MBChB, MSc, MD, PhD, of the Blizard Institute of Cell and Molecular Science at Queen Mary, University of London, London, UK, on behalf of the consortia. Environmental causes include drinking alcohol, smoking, and eating fatty foods.
They analyzed 660,000 genetic variations in 1,800 patients with Barrett's esophagus and tested the top 200,000 genetic variations in another set of 1,105 patients, comparing them with >5,000 controls without the disease.
The two single nucleotide polymorphisms (SNPs) that showed “compelling evidence for association” were tested in an additional 4,500 patients, and variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined 4.09 × 10−9; OR 1.21; 95% CI 1.13–1.28), within the MHC locus, and chromosome 16q24, rs9936833 (Pcombined 2.74 × 10−10; OR 1.14, 95% CI 1.10–1.19). The closest protein-coding gene for 16q24 is FOXF1, which is implicated in esophageal development and structure. Additional study found that SNPs associated with either body mass index or waist-hip ratio, predisposing to obesity, shared the same risk alleles in Barrett's esophagus.
“Our findings provide a basis for genetically screening 30% of the Western population who get acid reflux to see which 10% to 20% of them—3% of the population overall—will go on to develop Barrett's esophagus,” Dr. Jankowski stated. The genetic variations will also form the basis for developing a screening test for the disease and new targets for drug therapy.
An additional 10,000 patients will be tested to replicate these results and perhaps identify other genes that may predispose to Barrett's esophagus.