Gastric Cancer: Basic Aspects

Abstract

Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. In the last years, molecular oncobiology studies brought to light a number of genes that are implicated in gastric carcinogenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variants of the genes IL‐10, IL‐17, MUC1, MUC6, DNMT3B, SMAD4, and SERPINE1 have been reported to modify the risk of developing GC. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation (GSK3β, CD133, DSC2, P‐Cadherin, CDH17, CD168, CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through tumor suppressor gene inactivation mechanisms (TFF1, PDX1, BCL2L10, XRCC, psiTPTE‐HERV, HAI‐2, GRIK2, and RUNX3). It also addressed the role of the inflammatory mediator cyclooxygenase‐2 (COX‐2) in the process of gastric carcinogenesis and its importance as a potential molecular target for therapy.

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…This model assumes the sequence of precancerous lesions as a dynamic process from an initial superficial inflammation caused by Helicobacter pylori (H. pylori) infection to a fully malignant neoplasm of the stomach. Thus, the chronic infection of the gastric mucosa by the H. pylori, which colonize approximately 50% of the human population, is considered the strongest known risk factor for the development of gastric cancer [6,7] . Ooi et al [8] identified three signaling pathways (nuclear factor-kB, Wnt/b-catenin, and proliferation/stem cell) that were deregulated in more than 70% of the patients diagnosed with gastric cancer, resulting in increased inflammatory cytokine production, abnormal apoptosis, undesirable epithelial cell proliferation/differentiation, and epithelial cell transformation.…”

Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer

“…The high mortality of GC is explained by our poor understanding of its mechanism of progression and the lack of suitable diagnostic markers that hinder diagnosis before the disease reaches an advanced stage (7,8). GC represents a biologically and genetically heterogeneous group of tumours that are induced by multiple factors that deregulate cell signalling pathways, which leads to the acquisition of malignant phenotypes such as increased cell proliferation, inhibition of apoptosis and enhanced invasiveness (9)(10)(11). Identification of novel molecules is therefore required to improve diagnosis and therapy.…”

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

“…Helicobacter pylori (H. pylori) infection is involved in the early stage of gastric cancer pathogenesis by inducing chronic gastritis (3)(4)(5)(6). This chronic gastritis can persist for decades and may result in nonresolving inflammation, which is a major driver of gastric cancer (6), and the interaction of host-pathogen contributes to this carcinogenesis (7).…”