Page 130 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

1. Introduction
Gastric cancer remains a prevalent disease worldwide with a poor prognosis. Helicobacter pylori plays a major role in gastric carcinogenesis. H. pylori colonization leads to chronic gastritis, which predisposes to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually gastric cancer. Screening, treatment, and prevention of H. pylori colonization can reduce the incidence of gastric cancer[1]. Other interventions that may yield a similar effect, although of smaller magnitude, include promotion of a healthy lifestyle including dietary measures, non- smoking, low alcohol intake, and sufficient physical activity[2]. Furthermore, increasing evidence suggests that host factors, including genetic make-up, are also important determinants for carcinogenesis in H. pylori infection[3]. Colonization of H. pylori has been associated with chronic gastritis because it can trigger fulminant inflammatory response which can lead to pathological conditions such as Gastric carcinoma and peptic ulcer disease[4]. Consequently a clinical need exists to stratify H. pylori-infected patients with respect to their propensity to develop H. pylori- related pathology, especially for GC this is felt as a pressing concern. The importance of H. pylori virulence factors is evident from the serious clinical outcome associated with bacteria positive for the vacillating cytotoxic (vacA) and the cytotoxin-associated gene A (cagA) antigen[5]. However, these two virulence factors are insufficient to explain the variety in clinical presentation of pathology associates with H. pylori infection[6, 7]. A potential H. pylori virulence factor possibly important to explain this variance in clinical outcome is the cag pathogenicity island (cag-PAI). The cagA gene is a marker for the presence of the cag-PAI of approximately 40 kb, whose presence is associated with the more severe clinical outcomes.[8, 9] A type IV secretion system translocate cagA protein into gastric epithelial cells, where it is phosphorylated. When this modification occurs, cagA affects various cellular processes and signal transduction pathways, such as disruption of tight and adherent junctions that lead to pro-inflammatory and mitogenic responses–effects [8, 10]. One of the six cag-PAI genes is cagE, located in the right half of the cag-PAI, that has been shown to induce secretion of interleukin (IL)-8, from infected host epithelial cells[11, 12].
Another putative virulence factor is iceA, whose gene has two main allelic variants, iceA1 and iceA2. The expression of iceA1 is up-regulated on contact of H. pylori with human epithelial cells and may be linked with peptic ulcer disease.[13, 14] The blood group antigen binding adhesin (babA), a 78-KDa outer membrane protein
Chapter 6
Chapter 6
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