Molecular Pathways: Involvement of Helicobacter pylori–Triggered Inflammation in the Formation of an Epigenetic Field Defect, and Its Usefulness as Cancer Risk and Exposure Markers

Formation of epigenetic field for cancerization by chronic inflammation triggered by H. pylori infection. H. pylori infection induces acute inflammation, followed by chronic inflammation, formation of an epigenetic field for cancerization, and development of gastric cancers. Aberrant methylation is induced in driver genes (schematically represented by gene 1) and passenger genes (genes 3 and 4). Specific genes are methylated in gastric mucosae with H. pylori infection, and driver genes usually have very low methylation levels. On the other hand, passenger genes that have low or no expression in normal cells usually have high methylation levels. The methylation level of some passenger genes reflects the degree of accumulation of epigenomic damage, and correlates with gastric cancer risk. Chronic inflammation triggered by H. pylori infection is critical for methylation induction, and if data from a mouse colitis model are combined, the importance of monocytes can be speculated. As translational targets, methylation levels of specific genes in normal-appearing tissues can be used as a cancer risk marker that reflects a person's life. The methylation signature has potential as a marker for past exposure to specific environmental factors. Suppression of induction of aberrant DNA methylation, and possibly removal of accumulated aberrant methylation can be used for cancer prevention (shown in red).