Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma

Abstract

Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review.

Keywords: Environmental factors; Gastric cancer; Genetic polymorphism; Helicobacter pylori; Virulence factors.

Figure 1

The roles of the main virulence factors in pathogenesis of Helicobacter pylori infection[6]. Adherence of Helicobacter pylori to gastric epithelial cells is mediated by BabA and SabA binding Leb and Lewis x/a respectively. CagA is translocated into epithelial cells through T4SS, and then tyrosine phosphorylated at EPIYA sites by Src and Abl kinases. CagA contributes to alteration of myriad signaling transduction, which affects host cell physiology with disruption of intercellular junctions, loss of cell polarity, promotion of inflammation, dysregulation of cellular apoptosis and proliferation. VacA inducts cytoplasmic vacuolation, apoptosis and immune suppression[6].

Figure 2

The pathogenesis of Helicobacter pylori-associated gastric cancer. The pathogenesis of H. pylori-associated GC is a multi-factorial process, its development depends on a combination of host, bacterial and environmental factors, and the pathological changes might progress in steps. H. pylori: Helicobacter pylori; GC: Gastric cancer.