Genetic Biomarkers of Barrett's Esophagus Susceptibility and Progression to Dysplasia and Cancer: A Systematic Review and Meta-Analysis

Dig Dis Sci. 2016 Jan;61(1):25-38. doi: 10.1007/s10620-015-3884-5. Epub 2015 Oct 7.


Barrett's esophagus (BE) is a common and important precursor lesion of esophageal adenocarcinoma (EAC). A third of patients with BE are asymptomatic, and our ability to predict the risk of progression of metaplasia to dysplasia and EAC (and therefore guide management) is limited. There is an urgent need for clinically useful biomarkers of susceptibility to both BE and risk of subsequent progression. This study aims to systematically identify, review, and meta-analyze genetic biomarkers reported to predict both. A systematic review of the PubMed and EMBASE databases was performed in May 2014. Study and evidence quality were appraised using the revised American Society of Clinical Oncology guidelines, and modified Recommendations for Tumor Marker Scores. Meta-analysis was performed for all markers assessed by more than one study. A total of 251 full-text articles were reviewed; 52 were included. A total of 33 germline markers of susceptibility were identified (level of evidence II-III); 17 were included. Five somatic markers of progression were identified; meta-analysis demonstrated significant associations for chromosomal instability (level of evidence II). One somatic marker of progression/relapse following photodynamic therapy was identified. However, a number of failings of methodology and reporting were identified. This is the first systematic review and meta-analysis to evaluate genetic biomarkers of BE susceptibility and risk of progression. While a number of limitations of study quality temper the utility of those markers identified, some-in particular, those identified by genome-wide association studies, and chromosomal instability for progression-appear plausible, although robust validation is required.

Keywords: Barrett’s esophagus; Biomarkers; Esophageal cancer; Esophageal dysplasia; Genetic.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Barrett Esophagus / diagnosis
  • Barrett Esophagus / genetics*
  • Barrett Esophagus / therapy
  • Disease Progression
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / genetics*
  • Esophagus / pathology*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome-Wide Association Study
  • Humans
  • Phenotype
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / therapy
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome


  • Genetic Markers

Supplementary concepts

  • Adenocarcinoma Of Esophagus