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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2019; 25(30): 4105-4124
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4105
Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions
Anca Negovan, Mihaela Iancu, Emőke Fülöp, Claudia Bănescu
Anca Negovan, Department of Clinical Science-Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
Mihaela Iancu, Department of Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Cluj 400349, Romania
Emőke Fülöp, Department of Morphological Sciences, Histology, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
Claudia Bănescu, Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Mureș 540139, Romania
Author contributions: All authors contributed equally to this paper with conception and design of the study, literature review and analysis, and drafting, critically revising and editing of the manuscript, and giving approval of the final version.
Supported by an Internal Research Grant from the University of Medicine, Pharmacy, Sciences and Technology of Tâ rgu Mureș , No. 615/12/17.01.2019.
Conflict-of-interest statement: The authors declare no conflict of interest.
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/
Corresponding author: Mihaela Iancu, PhD, Lecturer, Department of Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, Louis Pasteur St, no. 6, Cluj-Napoca 400349, Romania. miancu@umfcluj.ro
Telephone: +4-074-0130888
Received: April 1, 2019
Peer-review started: April 2, 2019
First decision: May 5, 2019
Revised: July 12, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 14, 2019
Abstract

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.

Keywords: Helicobacter pylori, Gastritis, Premalignant, Glandular atrophy, Intestinal metaplasia, Single-nuclear polymorphism, Gene variants, Interleukins

Core tip: The role of cytokines and their gene variants has been questioned in relation to Helicobacter pylori (H. pylori) gastritis and gastric cancer but only infrequently for preneoplastic lesions. To date, only the single nucleotide polymorphisms IL-10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN appear to be predictors for premalignant gastric lesion susceptibility. In order to develop preventative strategies, further studies using multivariable models to test the modifying effect of H. pylori infection on the relationship between cytokine gene variants and premalignant lesions or to test the interaction between H. pylori and cytokine gene variants should be considered.