Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2460-2474
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2460
Molecular alterations in gastric cancer with special reference to the early-onset subtype
Małgorzata Skierucha, Anya NA Milne, G Johan A Offerhaus, Wojciech P Polkowski, Ryszard Maciejewski, Robert Sitarz
Małgorzata Skierucha, Ryszard Maciejewski, Robert Sitarz, Department of Human Anatomy, Medical University of Lublin, 20-950 Lublin, Poland
Anya NA Milne, Department of Pathology, Diakonessenhuis, 3582 KE Utrecht, The Netherlands
G Johan A Offerhaus, Department of Pathology, H04-312, University Medical Centre Utrecht, Post box 85500, 3508 GA Utrecht, The Netherlands
Wojciech P Polkowski, Robert Sitarz, Department of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, Poland
Robert Sitarz, Department of Pathology, H04-312, University Medical Centre Utrecht, Post box 85500, 3508 GA Utrecht, The Netherlands
Author contributions: Skierucha M and Sitarz R developed the concept of the research, collected the research data and wrote the paper; Offerhaus GJA, Milne ANA, Polkowski WP and Maciejewski R provided significant content and critically revised the manuscript.
Supported by A grant from the Polish Ministry of Science and Higher Education, No. N N402 423838.
Conflict-of-interest statement: The authors declare that they have 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/
Correspondence to: Robert Sitarz, MD, PhD, Department of Surgical Oncology, Medical University of Lublin, S. Staszica 11, 20-081 Lublin, Poland. r.sitarz@umlub.pl
Telephone: +48-661012882 Fax: +48-81-7406149
Received: September 22, 2015
Peer-review started: September 25, 2015
First decision: October 14, 2015
Revised: November 6, 2015
Accepted: December 30, 2015
Article in press: December 30, 2015
Published online: February 28, 2016
Abstract

Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.

Keywords: Gastric cancer, Early-onset gastric cancer, Molecular alterations, Chromosomal instability, Single-nucleotide polymorphism, Microsatellite instability, Epigenetic alterations, Loss of heterozygosity

Core tip: There are numerous factors that may trigger gastric carcinogenesis. They include genetic susceptibility, acquired mutations and favourable environmental circumstances, which combine and multiply within the lifetime. Therefore, the incidence of gastric cancer is the highest among the elderly. Conversely, young patients are exposed to environmental carcinogens for a short period, so they are a reliable subgroup in which to study primary genetic alterations. This review provides a summary of the data published thus far concerning the molecular characteristics of gastric cancer and highlights the outstanding features of early-onset gastric cancer.