Esophageal adenocarcinoma phenotypes and risk factors

Abstract

The incidence of esophageal adenocarcinoma (EAC) has increased significantly over the last several decades. The majority of EAC patients present without a prior history of Barrett's esophagus (BE). As a result, endoscopic surveillance has made a suboptimal impact on EAC survival. These concerns raise serious question whether the time has come to take a different direction. The aim of this article is to review evolving evidence of EAC phenotypes and risk factors. A recent study has identified two phenotypes of EAC based on the presence or absence of intestinal metaplasia (IM) in the background of the tumor (BE/IM and non-BE/IM). The study found that one-half of patients with EAC have the non-BE/IM phenotype, which is associated with more aggressive behavior and worse survival. A retrospective review demonstrates that the proportion of the two phenotypes has been stable over the last decades. Similarly, the increasing incidence of EAC cannot be explained by an increased frequency of new, unique risk factors but rather by a higher prevalence of already known risk factors. Emerging data also demonstrates that, whereas reflux symptoms are an unreliable feature for screening regardless of phenotype, the absence of reflux symptoms is more common for the non-BE/IM. Differences in the degree of genomic methylation and immune response might explain the two phenotypes at a genomic level. EAC phenotypes have implications for tumor behavior and phenotypic differences might underlie our suboptimal screening efforts. Future screening efforts should not uniformly rely on reflux symptoms as a prerequisite for screening and should consider alternatives to the current screening strategy.