Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach

Abstract

Purpose: Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori - infected individuals, we tested whether eradication of H. pylori alters the methylation status of the noncancerous gastric epithelium. Experimental Design: Endoscopic biopsies were taken from the antrum and corpus of H. pylori - infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H. pylori eradication. Results: Among the 28 H. pylori - infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H. pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001). Conclusion: Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori - infected individuals. Eradication of H. pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation. © 2006 American Association for Cancer Research.