Normal gastric tissueHelicobacter pyloriinfection is associated with epigenetic age acceleration, increased mitotic tick rate, tissue cell composition, and Natural Killer cell methylation alterations

Abstract

AbstractBackgroundGastric adenocarcinomas are a leading cause of global mortality, associated with chronic infection withHelicobacter pylori. The mechanisms by which infection withH. pyloricontributes to carcinogenesis are not well understood. Recent studies from subjects with and without gastric cancer have identified significant DNA methylation alterations in normal gastric mucosa associated withH. pyloriinfection and gastric cancer risk. Here we further investigated DNA methylation alterations in normal gastric mucosa in gastric cancer cases (n = 42) and control subjects (n = 42) withH. pyloriinfection data. We assessed tissue cell type composition, DNA methylation alterations within cell populations, epigenetic aging, and repetitive element methylation.ResultsIn normal gastric mucosa of both gastric cancer cases and control subjects, we observed increased epigenetic age acceleration associated withH. pyloriinfection. We also observed an increased mitotic tick rate associated withH. pyloriinfection in both gastric cancer cases and controls. Significant differences in immune cell populations associated withH. pyloriinfection in normal tissue from cancer cases and controls were identified using DNA methylation cell type deconvolution. We also found natural killer cell-specific methylation alterations in normal mucosa from gastric cancer patients withH. pyloriinfection.ConclusionsOur findings from normal gastric mucosa provide insight into underlying cellular composition and epigenetic aspects ofH. pyloriassociated gastric cancer etiology.