Open AccessRole of nitric oxide in the pathogenesis of Barrett’s-associated carcinogenesis
Author(s) -
Gen Kusaka,
Kaname Uno,
Katsunori Iijima,
Tooru Shimosegawa
Publication year - 2016
Publication title -
world journal of gastrointestinal pathophysiology
Language(s) - English
Resource type - Journals
ISSN - 2150-5330
DOI - 10.4291/wjgp.v7.i1.131
Subject(s) - medicine , carcinogenesis , esophagus , reflux esophagitis , gastroenterology , barrett's esophagus , gerd , nitric oxide , cdx2 , adenocarcinoma , esophagitis , intestinal metaplasia , cancer research , reflux , stomach , cancer , biology , transcription factor , disease , homeobox , biochemistry , gene
Barrett's esophagus (BE), a premalignant condition to Barrett's adenocarcinoma (BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2 (CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide (NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastro-esophageal junction (GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.