Normal gastric mucosa from gastric cancer cases and healthy controls exhibit methylome-wide changes associated with current and past Helicobacter pylori infection and cancer risk

Aim: We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and whether these changes constitute cancer risk. Method: The Infinium HumanMethylation450 BeadChip Kit was used to assess methylation Results: We found 1924 differentially methylated positions (DMPs) and 438 differentially methylated regions (DMRs) associated with H. pylori infection, most of which were hypermethylated. Significant methylation alterations identified in the initial sample set were replicated in a second validation set. The H. pylori-associated DMP/Rs showed marked stability after H. pylori clearance. Furthermore, we found 152 DMRs associated with cancer risk, regardless of H. pylori status. A methylation score derived using three biomarkers was a strong predictor of GC, with an area under the curve of 0.765. Normal gastric mucosa samples from GC cases (n = 42) and controls (n = 42), nested in a large case-control study and stratified by H. pylori status, were subjected to genome-wide methylation profiling and genotyping. A validation set of gastric mucosa samples (n=180) was used in the replication phase