Esophageal adenocarcinoma (EAC) is the esophageal cancer that arises in the distal esophagus from Barrett’s metaplasia, the replacement of the normal squamous lining by intestinal-type columnar cells.
EAC is the second most common esophageal cancer worldwide, but in Western countries it has become the most common form. The change is recent: until about 1994, ESCC was also the most common type in those countries, and the shift towards EAC followed the rising incidence of gastroesophageal reflux disease (GERD), the main risk factor for EAC. Better surveillance facilities, such as esophagogastroduodenoscopy (EGDS), may also have contributed by detecting more cases.
Risk factors
As in ESCC, tobacco smoking raises the risk of EAC. The central driver, however, is chronic reflux. GERD damages the squamous epithelium and pushes it towards aberrant metaplasia, converting the cells into intestinal-type cells that are more prone to cancer. The consequence is a strong association: patients with Barrett’s esophagus are 10- to 55-fold more likely to develop EAC.
Obesity raises the risk in two ways. Abdominal obesity increases the risk of GERD and Barrett’s esophagus, which raises the risk of EAC indirectly, but abdominal obesity itself can also raise the risk of EAC directly.
Several factors appear protective against EAC. H. pylori infection is associated with a 50% reduction in risk, and NSAID use also appears protective. Proton pump inhibitors lower the risk of progression of Barrett’s esophagus to cancer by 71%, and a diet rich in fruit and vegetables is protective as well.
How it develops
The pathogenesis of EAC rests on the inflammatory microenvironment in Barrett’s mucosa, together with the accumulation of mutations that drive the progression from Barrett’s esophagus to cancer.
The genetic change with the clearest clinical relevance is amplification or overexpression of HER2 (human epidermal growth factor receptor 2, also called ERBB2). HER2 positivity is associated with a poorer prognosis, because the tumor becomes less dependent on external growth signals, and it also makes the tumor a candidate for HER2-directed treatment.