Reversal of E-Cadherin Promoter Hypermethylation Status after Helicobacter pylori Eradication

Abstract

BACKGROUND: E-cadherin hypermethylation plays an important role in gastric carcinogenesis. Reversing hypermethyation may halt carcinogenic process. We have previously reported that Helicobacter pylon infection is an independent factor for predicting E-cadherin methylation in chronic gastritis in patients without gastric cancer. AIM: to examine if eradication of H. pylori could reverse E-cadherin methylation. METHODS: Patients with dyspepsia and H. pylori infection were randomized to receive H. pylori eradication therapy (Group 1, n = 41) or no treatment (Group 2, n = 40) and followed up prospectively. Gastric mucosae were taken for methylation assay at Week 0 (before treatment) and Week 6 (after treatment). Archived specimens with intestinal metaplasia with H. pylori infection (n = 22) and without (n = 19) were also retrieved for methylation analysis. Methylation was assessed using methylation specific PCR. RESULTS: Methylation was detected in 46% (19/41) and 17% (7/41) at Week 0 and 6, respectively in Group 1 (P = 0.004). 78.9% (15/19) specimens turned un-methylated after eradicating H. pylori. The disappearing of methylation did not depend on the reversal of chronic gastritis to normal mucosa, as only one chronic gastritis specimen with positive methylation reversed to normal mucosa and showed negative methylation after H. pylon eradication. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) at Week 0 and 6, respectively in Group 2 (P = 0.5). Methylation frequency did not differ in H. pylori positive or negative intestinal metaplastic specimens (72.7% vs 63%, P = 0.5). CONCLUSION: H. pylon eradication therapy could reverse methylation in patients with chronic gastritis and may halt the process of gastric carcinogenesis.