Fig. 2

Methylation induction by Helicobacter pylori infection and gastric cancer risk. a Schematic representation of methylation levels in the gastric mucosae of individuals with and without gastric cancer, and with and without H. pylori infection. Methylation levels were measured in DNA extracted from gastric biopsy specimens. Without H. pylori infection, there is a significant difference between healthy volunteers (group 1) and gastric cancer cases (group 2). With H. pylori infection, the methylation level is high in both healthy volunteers (group 3) and gastric cancer cases (group 4). H. pylori-positive individuals had higher methylation levels than H. pylori-negative gastric cancer cases, most of whom were considered to have had prior exposure to H. pylori infection. Modified from Maekita et al. [22]. b A hypothetical temporal profile of gastric methylation levels during the course of H. pylori infection in years to decades. Time point 1: Without H. pylori infection, the methylation is initially. Time points: 2–5, H. pylori infection induces both permanent (closed box) and temporary (open box) components of methylation, and the total methylation level fluctuates due to fluctuation of the temporary component. Time points 6–8: after H. pylori infection discontinues, the temporary component disappears, and the increase in the permanent component stops. It is speculated that the permanent component is due to methylation in stem cells and that the temporary component is due to methylation in progenitor and differentiated cells. The permanent component is correlated with damage in stem cells, and thus with gastric cancer risk