Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2016; 8(1): 40-54
Published online Jan 15, 2016. doi: 10.4251/wjgo.v8.i1.40
Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike
Natale Figura, Luigi Marano, Elena Moretti, Antonio Ponzetto
Natale Figura, Department of Medical, Surgical and Neurological Sciences, University of Siena and Policlinico S. Maria alle Scotte, 53100 Siena, Italy
Luigi Marano, General, Minimally Invasive and Robotic Surgery, Department of Surgery, Hospital San Matteo degli Infermi, 06049 Spoleto, Perugia, Italy
Elena Moretti, Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
Antonio Ponzetto, Department of Medical Sciences, University of Torino, 10126 Torino, Italy
Author contributions: All the authors contributed equally in the design of the review, acquisition and interpretation of data and drafting the manuscript, which was approved by them all.
Conflict-of-interest statement: The authors have no conflict of interest or financial ties to disclose.
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:
Correspondence to: Natale Figura, Professor, Department of Medical, Surgical and Neurological Sciences, University of Siena and Policlinico S. Maria alle Scotte, Viale Bracci, 53100 Siena, Italy.
Telephone: +39-5-77585463 Fax: +39-5-77233446
Received: June 14, 2015
Peer-review started: June 17, 2015
First decision: August 4, 2015
Revised: October 6, 2015
Accepted: November 3, 2015
Article in press: November 4, 2015
Published online: January 15, 2016

Gastric carcinoma (GC) develops in only 1%-3% of Helicobacter pylori (H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host’s factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C’-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta (IL-1β) group and tumour necrosis factor-alpha (TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability (MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes (such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.

Keywords: Helicobacter pylori infection, CagA, CagA gene polymorphism, Haplotype, Human gene mutation, Gene methylation, Gastric carcinoma, Inflammatory cytokine

Core tip: CagA and the cagA types may play different roles in the intestinal and diffuse histotypes of gastric carcinoma (GC); The current criteria of Helicobacter pylori (H. pylori) strain classification based on their carcinogenic potential gave rise to confusion and should be unified. The possible role of inflammatory cytokine haplotypes in GC development should be reassessed taking into account some host’s factors, the most important being different ethnic origin. Infection by the cagA positive H. pylori genotype may determine an increased inflammatory response and a consequent enhancement of mutagenesis rate, oxidative-stress, reactive oxygen species generation, dysfunction of DNA repair mechanisms, genetic instability and resultant high risk of GC development.