Risk Factors for the Development of Barrett's Esophagus and Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis

Abstract

Background: Barrett's esophagus (BE) is the most widely established precursor to esophageal adenocarcinoma (EAC). Despite current screening guidelines, more than 90% of EAC patients lack a previous diagnosis of BE. We performed a systematic review and meta-analysis to identify the most important risk factors for the development of BE or EAC.

Recent findings: PubMed.gov, Ovid Medline, Embase, and Cochrane Library were searched through March 15, 2024. Studies comparing characteristics of patients with endoscopically diagnosed BE or EAC to control groups satisfied our inclusion criteria. Dual extraction provided data for random-effects meta-analyses. Sufficient data were extracted from 54 included studies to perform our meta-analyses. There were five risk factors with significant associations for the development of BE: symptoms of gastroesophageal reflux at least once weekly (OR, 3.56; 95% confidence interval [CI], 2.03-6.25; p = 0.004) tobacco smoking (OR, 1.41; 95% CI, 1.30-1.51; p < 0.001); alcohol use (OR, 1.37; 95% CI, 1.10-1.71; p = 0.008); male gender (OR, 1.36; 95% CI, 1.19-1.57; p < 0.001); and obesity (BMI > 30 kg/m²) (OR, 1.23; 95% CI, 1.09-1.39; p = 0.003). Tobacco smoking was significantly associated with the diagnosis of EAC (OR, 2.15; 95% CI, 1.85-2.43; p < 0.001).

Conclusion: Five risk factors showed significant associations with the development of BE and one with the development of EAC, with over a three-fold increase in BE for patients with gastroesophageal reflux more than once weekly. These data could prove useful in developing diagnostic paradigms with higher emphasis on patients experiencing more frequent acid reflux.

Keywords: Barrett's esophagus; cancer epidemiology; cancer screening; early detection; esophageal adenocarcinoma; gastroesophageal reflux.

FIGURE 1

PRISMA flow diagram.

FIGURE 2

Forest plots for outcomes data. (A) Forest plot of pooled OR for male gender as a risk factor for being diagnosed with BE. (B) Forest plot of the pooled OR for male sex as a risk factor for being diagnosed with EAC. (C) Forest plot of the pooled OR for obesity as a risk factor with being diagnosed BE. (D) Forest plot of pooled OR for tobacco smoking as a risk factor for being diagnosed with BE. (E) Forest plot of pooled OR for tobacco smoking as a risk factor for being diagnosed with EAC. (F) Forest plot of pooled OR for reflux more than once weekly as a risk factor for being diagnosed with BE. (G) Forest plot of pooled OR for alcohol use as a risk factor for being diagnosed with BE. (H) Forest plot of pooled OR for alcohol use as a risk factor for being diagnosed with EAC.