Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma

Epigenetic influences, such as DNA methylation, histone acetylation, and up-regulation/down-regulation of genes by microRNAs, change the genetic makeup of an individual without affecting DNA base-pair sequences. Indeed, epigenetic changes play an integral role in the progression from normal esophageal mucosa to Barrett's esophagus to esophageal adenocarcinoma via dysplasia-metaplasia-neoplasia sequence. Many genes involved in esophageal adenocarcinoma display hypermethylation, leading to their down-regulation. The classes of these genes include cell cycle control, DNA and growth factor repair, tumor suppressors, antimetastasis, Wnt-related genes, and proapoptotic genes. Histone acetylation in the pathophysiology of esophageal diseases has not been thoroughly investigated, and its critical role in the development of esophageal adenocarcinoma is less defined. Many microRNAs have been associated with the development of Barrett's esophagus and esophageal adenocarcinoma. Here, we critically addressed the specific steps most closely influenced by microRNAs in the progression from Barrett's esophagus to esophageal adenocarcinoma. However, microRNAs can target up to hundreds of genes, making it difficult to correlate directly with a given phenotype of the disease. Esophageal adenocarcinoma progressing from premalignant condition of Barrett's esophagus carries an extremely poor prognosis. Risk stratification for patients based on their epigenetic profiles may be useful in providing more targeted and directed treatment to patients.