Helicobacter pylori and molecular events in precancerous gastric lesions

Abstract

SUMMARYGastric cancer can be divided into intestinal type and diffuse type that differ substantially in epidemiology and pathogenesis. The most important aetiological factor associated both with intestinal and diffuse gastric cancer, is Helicobacter pylori. Exposure of gastric epithelial cells to H. pylori results in an inflammatory reaction with the production of reactive oxygen species and nitric oxide that, in turn, deaminates DNA causing mutations. The complex interplay between H. pylori strain, inflammation and host characteristics may directly promote diffuse type gastric cancer or induce a cascade of morphological events, i.e. atrophy, intestinal metaplasia and dysplasia, finally leading to intestinal type gastric cancer. Two mechanisms, genetic and epigenetic have been held to play a role in the molecular alterations underlying gastric carcinogenesis. The former, comprising changes in the DNA sequence, is irreversible; the latter, involving DNA methylation, is potentially reversible by eliminating the triggering agents. If H. pylori is eradicated before development of stable mutations, the risk of gastric cancer will likely be prevented. Thus, eradication of H. pylori might immediately reduce the risk of diffuse type gastric cancer, whereas prevention of intestinal type gastric cancer may be less effective if patients are treated later in the evolution of the carcinogenic process.

MDR1-P-glycoprotein behaves as an oncofetal protein that promotes cell survival in gastric cancer cells

“…Another aliquot was exposed to 3% H 2 increased level of nitric oxide synthase that exposes the cells to a significant oxidative stress. 31 The cells with high levels of P-gp and Bcl-x L could escape stress-imposed death and accumulate DNA damage ultimately leading to cell transformation and cancer development. Opposite, the eradication of the Hp infection with the concomitant resolution of gastric inflammation may lead to the downregulation or even suppression of P-gp expression.…”

Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis

“…Regarding the H. pylori-related carcinogenesis, distinct pathways have been proposed for two histological types of gastric cancer: intestinal type and diffuse type [36]. Intestinal-type cancer is considered to develop in a multistep process starting from chronic active gastritis and progressing through chronic atrophic gastritis, intestinal metaplasia, and dysplasia [37].…”

Correlation between negative expression of pepsinogen C and a series of phenotypic markers of gastric cancer in different gastric diseases

“…Likewise, carcinogenesis of GC is a multistep process initiated by chronic superficial gastritis (nonatrophic gastritis, SG), followed by atrophic gastritis (AG), then intestinal metaplasia (IM), and finally by dysplasia and adenocarcinoma 4, 5. Atrophic gastritis (clinical terminology), intestinal metaplasia, and dysplasia (histopathological terminology) are well‐established premalignant conditions of GC 6, 7, 8. Effective management of AG, IM, and dysplasia is a very important way to prevent GC.…”