Gastric Cancer Risk Prediction Using Epigenetic Alterations Accumulated in Noncancerous Gastric Tissues

Risk prediction for gastric cancer (GC) is important, especially for H. pylori-eradicated individuals whose number is rapidly increasing in Japan. For accurate cancer risk prediction, analysis of epigenetic changes, particularly aberrant DNA methylations, has a great potential. It is induced in the gastric mucosa by H. pylori infection, persists for life, and is causally involved in gastric carcinogenesis. The DNA methylation levels in individuals without current H. pylori infection correlate with GC risk and have a greater impact than that of accumulated point mutations. A methylation marker is necessary to assess the overall epigenomic damage accumulated in the genome of gastric epithelial cells. Initially, CpG islands methylated in GC cells were used. More informative markers were then isolated by an analysis of the gastric mucosa of gastric cancer patients and healthy individuals. Finally, highly informative markers unaffected by contaminating blood cells have been developed using an advanced technology and a screening algorithm. With an aim of bringing epigenetic cancer risk diagnosis into practice, we first conducted a multicenter prospective cohort study for risk prediction of metachronous GC among GC patients who had undergone endoscopic treatment and achieved the first proof of concept. We are currently conducting a new, nationwide study for risk prediction of primary GC among healthy H. pylori-eradicated individuals. Epigenetic cancer risk diagnosis, which was initially developed for GC and potentially applicable to other inflammation-associated cancers, has a great potential to contribute to precision medicine.