Valenzuela MA, Canales J, Corvalán AH, Quest AF. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World J Gastroenterol 2015; 21(45): 12742-12756 [PMID: 26668499 DOI: 10.3748/wjg.v21.i45.12742]
Corresponding Author of This Article
Andrew FG Quest, PhD, Cellular Communication Laboratory, Center for Molecular Studies of the Cell, Advanced Center for Chronic Diseases, School of Medicine, Universidad de Chile, Av. Independencia 1027, Santiago 8380453, Chile. aquest@med.uchile.cl
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Dec 7, 2015; 21(45): 12742-12756 Published online Dec 7, 2015. doi: 10.3748/wjg.v21.i45.12742
Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis
Manuel A Valenzuela, Jimena Canales, Alejandro H Corvalán, Andrew FG Quest
Manuel A Valenzuela, Jimena Canales, Andrew FG Quest, Laboratorio de Comunicaciones Celulares, Centro de Estudios Moleculares de la Célula, Programa de Biología Celular y Molecular, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
Manuel A Valenzuela, Jimena Canales, Alejandro H Corvalán, Andrew FG Quest, Cellular Communication Laboratory, Center for Molecular Studies of the Cell, Advanced Center for Chronic Diseases, School of Medicine, Universidad de Chile, Santiago 8380453, Chile
Alejandro H Corvalán, UC - Centro de Investigación en Oncología, Pontificia Universidad Católica de Chile, Santiago 8330034, Chile
Alejandro H Corvalán, Departamento de Hematología-Oncología, Facultad de Medicine, Pontificia Universidad Católica de Chile, Santiago 8330074, Chile
Author contributions: Valenzuela MA and Quest AFG wrote and edited the review, designed its structure and made conceptual revisions of the different sections; Canales J contributed with a bibliographic revision and discussion in the section “Genes modified by methylation upon H. pylori infection”, and also designed Figure 1; Corvalán AH contributed with the discussion in the section “Reprimo as a model for epigenetic changes in tumor suppressor genes in gastric cancer” and the clinical findings concerning miRNA biology.
Supported by CONICYT-FONDAP project, No. 15130011 (to Corvalánand AH and Quest AFG); FONDECYT project, No. 1151411 (to Corvalán AH); and a CONICYT PhD fellowship award (to Canales J).
Conflict-of-interest statement: Authors declare no conflict of interests for this article
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrew FG Quest, PhD, Cellular Communication Laboratory, Center for Molecular Studies of the Cell, Advanced Center for Chronic Diseases, School of Medicine, Universidad de Chile, Av. Independencia 1027, Santiago 8380453, Chile. aquest@med.uchile.cl
Telephone: +56-2-27382015 Fax: +56-2-27382015
Received: May 27, 2015 Peer-review started: May 29, 2015 First decision: July 14, 2015 Revised: August 8, 2015 Accepted: October 13, 2015 Article in press: October 13, 2015 Published online: December 7, 2015 Processing time: 193 Days and 5.3 Hours
Abstract
The sequence of events associated with the development of gastric cancer has been described as “the gastric precancerous cascade”. This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.
Core tip:Helicobacter pylori infection increases the risk of developing gastric cancer. Intestinal type gastric cancer is characterized by a histological cascade in which aberrant methylation of CpG islands and deregulation of microRNAs are observed. An exacerbated host response and bacterial virulence factors contribute to these epigenetic changes by enhancing DNA methyl transferase activity via nitric oxide production and silencing of tumor suppressor genes and miRNAs. Interestingly, methylated Reprimo DNA is detectable in blood samples and is potentially useful as an early detection marker. Finally, also the role of gamma glutamyl transpeptidase related mechanisms in the loss of the anti-apoptotic protein Survivin and gastric carcinogenesis is discussed.
