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Effects of Helicobacter pylori Eradication on Methylation Status of E-Cadherin Gene in Noncancerous Stomach

Authors' Affiliations: ¹ Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong and ² Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas

Requests for reprints: Wai K. Leung, Department of Medicine and Therapeutics, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong. Phone: 852-2632-3140; Fax: 852-2637-3852; E-mail: wkleung{at}cuhk.edu.hk.

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.

Commentary

Coming Unglued

Richard M. Peek, Jr., Barbara G. Schneider, and Pelayo Correa
Clin. Cancer Res. 2006 12: 2951-2954. [Full Text] [PDF]

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