Mechanisms and pathophysiology of Barrett oesophagus

Barrett oesophagus, in which a metaplastic columnar mucosa that can predispose individuals to cancer development lines a portion of the distal oesophagus, is the only known precursor of oesophageal adenocarcinoma, the incidence of which has increased profoundly over the past several decades. Most evidence suggests that Barrett oesophagus develops from progenitor cells at the oesophagogastric junction that proliferate and undergo epithelial-mesenchymal transition as part of a wound-healing process that replaces oesophageal squamous epithelium damaged by gastroesophageal reflux disease (GERD). GERD also seems to induce reprogramming of key transcription factors in the progenitor cells, resulting in the development of the specialized intestinal metaplasia that is characteristic of Barrett oesophagus, probably through an intermediate step of metaplasia to cardiac mucosa. Genome-wide association studies suggest that patients with GERD who develop Barrett oesophagus might have an inherited predisposition to oesophageal metaplasia and that there is a shared genetic susceptibility to Barrett oesophagus and to several of its risk factors (such as GERD, obesity and cigarette smoking). In this Review, we discuss the mechanisms, pathophysiology, genetic predisposition and cells of origin of Barrett oesophagus, and opine on the clinical implications and future research directions. In this Review, Souza and Spechler describe the mechanisms, pathophysiology and cells of origin of Barrett oesophagus, a precursor of oesophageal adenocarcinoma, and discuss the clinical implications.

Automated summary

Barrett's esophagus, a precursor of esophageal adenocarcinoma, is characterized by metaplastic columnar mucosa lining a portion of the distal esophagus. It is believed to develop from progenitor cells at the esophagogastric junction that undergo epithelial-mesenchymal transition as part of a wound-healing process. Gastroesophageal reflux disease (GERD) plays a role in the development of Barrett's esophagus by inducing reprogramming of key transcription factors in the progenitor cells. Genome-wide association studies suggest a shared genetic susceptibility between Barrett's esophagus and its risk factors, such as GERD, obesity, and cigarette smoking.