Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis

Abstract

The sequence of events associated with the development of gastric cancer has been described as "the gastric precancerous cascade". This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.

Status of Epstein-Barr Virus Coinfection withHelicobacter pyloriin Gastric Cancer

“…H. pylori are considered as major factors of GC, and aberrant methylation is also the hallmark of H. pylori -related GC [194]. Hypermethylation has been linked to H. pylori -related gastritis and inflammation [195]. The mechanisms of H. pylori induced hypermethylation are unknown and it is also thought that there is possible involvement of ROS/NOS [196].…”

Helicobacter pylori infection‐induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications

“…GC can be subdivided into intestinal type and diffuse type based on Lauren's classification . The development of noncardia intestinal‐type GC follows a well‐defined histological sequence of progression in Helicobacter pylori ( H. pylori, Hp )‐infected gastric mucosa, initiating as chronic gastritis followed by atrophy, intestinal metaplasia, dysplasia, and GC . H. pylori infection is the known single most important factor for GC, and eradication of H. pylori not only cures gastritis but also prevents the progression to long‐term complications, such as atrophic gastritis, intestinal metaplasia, recurrence of ulcers and reduces the incidence of GC.…”

The Role of Escherichia coli in the Development and Progression of Cancer

“…The origin of chronic inflammation has been associated to bacterial and virus infections, such as Helicobacter pylori (19), and papillomavirus (20). Nevertheless, the precise mechanism by which chronic inflammation triggers the development of cancer is not entirely clear; but it has been suggested that inflammation is not sufficient to trigger a cancer event and bacteria are required.…”