Helicobacter pylori in gastric carcinogenesis: mechanisms

Abstract

Helicobacter pylori infection induces chronic inflammation and is the strongest known risk factor for gastric cancer. The genomes of H pylori are highly diverse and therefore bacterial virulence factors play an important role in determining the outcome of H pylori infection, in combination with host responses that are augmented by environmental and dietary risk factors. It is important to gain further understanding of the pathogenesis of H pylori infection to develop more effective treatments for this common but deadly malignancy. This review focuses on the specific mechanisms used by H pylori to drive gastric carcinogenesis.

Figure 1

Gastric cancer is a result of a complex interplay between bacterial virulence factors, host inflammatory responses, and environmental influences. A. H. pylori virulence factors including SabA, BabA, CagA, and VacA influence the outcome of H. pylori infection, with CagA and VacAs1m1 types associated with increased disease severity. H. pylori disrupts the apical-junctional complex at the level of the tight junction (TJ) and adherens junction (AJ), and disrupts cell polarity. Disruption of the adherens junction results in translocation of β-catenin and p120 to the nucleus, altering transcription of genes that promote disease progression. Host genetic diversity also contributes to gastric cancer, including polymorphisms within IL-1β, TNFα, IL-10 and IL-32. B. Host iron (Fe) levels and salt (NaCl) concentrations also impact the virulence of H. pylori. High salt increases CagA production and low iron levels augment assembly of T4SS pili, increase CagA translocation, and augment IL-8 secretion.