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Determination of risk for Barrett's esophagus and esophageal adenocarcinoma. PURPOSE OF REVIEW: The incidence of esophageal adenocarcinoma and its precursor, Barrett's esophagus, have increased greatly over the past 40 years and continue to rise. This report summarizes the most recent data on the risk factors for Barrett's esophagus and esophageal adenocarcinoma. RECENT FINDINGS: Other factors, highly correlated with increasing trends for obesity, are the dominant driver of the increase in incidence of esophageal adenocarcinoma, interacting with gastroesophageal reflux disease symptoms. Abdominal obesity, independently of gastroesophageal reflux disease symptoms, is associated with increased risk of Barrett's esophagus and this association is likely mediated by high levels of leptin and insulin. Use of aspirin, nonsteroidal anti-inflammatory drugs, statins, and proton pump inhibitors are associated with a reduced risk of Barrett's esophagus as well as lower risk of neoplastic progression in patients with Barrett's esophagus. An increasing number of genetic loci have been associated with risk of Barrett's esophagus and esophageal adenocarcinoma. SUMMARY: Recent advances in identifying risk factors and reporting of more precise estimates of effect for the main risk factors will positively impact clinical risk stratification efforts for Barrett's esophagus and esophageal adenocarcinoma. Large pooling studies are underway to derive and validate reliable clinical risk models.