Esophageal adenocarcinoma arising in metaplastic Barrett's esophagus is one of the most rapidly increasing cancers in Western countries. Accumulating epidemiological evidence provides support that both chronic reflux injury and being overweight are strongly associated with the risk of esophageal adenocarcinoma. It is proposed that being overweight could contribute to increased predisposition to reflux by mechanically disrupting the physiological mechanisms that prevent reflux injury to the esophagus. Furthermore, mechanistic investigations also provide a link between being overweight to the risk of esophageal adenocarcinoma through increased loco-systemic injury response and metabolic syndrome. Together these observations provide the basis for the hypothesis that being overweight could be a key early trigger for the initiation and an ongoing stimulus for the progression of esophageal adenocarcinoma. In this chapter we will summarize the existing data that supports this hypothesis and discuss ongoing and future investigations to address this hypothesis that links obesity to risk of esophageal adenocarcinoma.
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