Obesity and increased risk of esophageal adenocarcinoma.

There has been a substantial increase in the incidence of esophageal adenocarcinoma over the past 40 years. Meta-analyses of large prospective cohorts and population-based case-control studies demonstrate consistent associations between obesity and the development of adenocarcinoma of the esophagus and esophago-gastric junction, with an approximate doubling of risk of esophageal adenocarcinoma among patients who are obese, and an almost five-fold increased risk among those with BMI >40 kg/m. The pathologic precursor, specialized intestinal metaplasia in Barrett's esophagus, is also associated with increased adiposity. Epidemiologic evidence suggests that this cancer risk is not solely due to increased gastro-esophageal reflux, and that adipose tissue itself, in particular visceral adipose, may fuel carcinogenesis through the production of adipokines, cytokines, growth factors, and increased inflammation. The robust epidemiologic evidence linking obesity with esophageal adenocarcinoma makes it an exemplar model for investigating the molecular mechanisms underpinning obesity-associated malignant progression, which are discussed in this review.