Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma

Abstract

Chronic gastric infection by the gram-negative bacterium Helicobacter pylori is strongly associated with the development of distal gastric carcinoma and gastric mucosal lymphoma in humans. Eradication of H. pylori with combination antibiotic therapy cures most cases of gastric lymphoma and slows progression to gastric adenocarcinoma. H. pylori promotes gastric neoplasia, principally via the induction of an intense gastric inflammatory response that lasts over decades. This persistent inflammatory state produces chronic oxidative stress and adaptive changes in gastric epithelial and immune cell pathobiology that in a minority of infected subjects eventually proceeds to frank neoplastic transformation.

Figure 1

Determinants of H. pylori-induced gastric carcinogenesis. Factors contributing to increased risk of gastric cancer following infection with H. pylori are (1) certain host genetic polymorphisms, (2) H. pylori virulence factors, including those translocated inside epithelial cells via the type 4 secretory system shown in green, (3) the host immune response, (4) the recruitment of bone-marrow derived cells into the gastric mucosa and (5) high intragastric luminal pH.

Figure 2

In the conventional model of H. pylori-associated carcinogenesis (left), the bacterium and associated inflammatory response stimulate increased cellular turnover and oxidative stress that promote oncogenic mutations, epigenetic changes and altered gene expression in epithelial cells. An alternative model (right) implicates Helicobacter species as the initiator of a chronic inflammatory response that recruits bone marrow derived cells to the gastric mucosa, contributing directly to the gastric neoplasm.