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The risk of gastric cancer (GC) declines after  Helicobacter pylori  ( H .  pylori ) eradication and long-term aspirin use. We evaluated the effects of  H .  pylori  eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as  miR- 3 4c ,  miR-124a-3 ,  miR- 129 - 2, and  miR-1 3 7 , in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1,  H .  pylori  eradication was associated with a significant reduction of  miR-124a-3  methylation only in non-IM, but not in IM.  miR-129-2  methylation in non-IM may be a surrogate marker of GC in  H .  pylori -infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of  H .  pylori  infection.  miR-129-2  methylation in non-IM was an independent predictive marker of GC in  H .  pylori -infected but not -eradicated patients. These results indicate that  H .  pylori  eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene.

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DNA methylation silencing of microRNA gene methylator in the precancerous background mucosa with and without gastric cancer: Analysis of the effects of H. pylori eradication and long-term aspirin use