Korean J Gastroenterol.  2016 Nov;68(5):253-259. 10.4166/kjg.2016.68.5.253.

Helicobacter pylori Eradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

• Choi J
• Kim SG
• Kim BG
• Koh SJ
• Kim JW
• Lee KL

• KMID: 2383502
• DOI: http://doi.org/10.4166/kjg.2016.68.5.253

Abstract

BACKGROUND/AIMS
Helicobacter pylori infection induces aberrant DNA methylation in gastric mucosa. We evaluated the long-term effect of H. pylori eradication on promotor CpG island hypermethylation in gastric carcinogenesis.
METHODS
H. pylori-positive patients with gastric adenoma or early gastric cancer who underwent endoscopic resection were enrolled. According to H. pylori eradication after endoscopic resection, the participants were randomly assigned to H. pylori eradication or non-eradication group. H. pylori-negative gastric mucosa from normal participants provided the normal control. CpG island hypermethylation of tumor-related genes (p16, CDH1, and RUNX-3) was evaluated by quantitative MethyLight assay in non-tumorous gastric mucosa. The gene methylation rate and median values of hypermethylation were compared after one year by H. pylori status.
RESULTS
In H. pylori-positive patients, hypermethylation of p16 was found in 80.6%, of CDH1 in 80.6%, and of RUNX-3 in 48.4%. This is significantly higher than normal control (p16, 10%; CDH1, 44%; RUNX-3, 16%) (p<0.05). In the H. pylori eradication group, methylation rates of p16 and CDH1 decreased in 58.1% and 61.3% of the patients, and the median values of hypermethylation were significantly lower at one year compared with the non-eradication group. However, RUNX-3 hypermethylation did not differ significantly at one year after H. pylori eradication. The non-eradication group hypermethylation did not change after one year.
CONCLUSIONS
H. pylori infection was associated with promotor hypermethylation of genes in gastric carcinogenesis, and H. pylori eradication might reverse p16 and CDH1 hypermethylation.

Keyword

Helicobacter pylori; CpG hypermethylation; p16; CDH1; Carcinogenesis

MeSH Terms

Adenoma
Carcinogenesis*
CpG Islands*
DNA Methylation
Gastric Mucosa
Helicobacter pylori*
Helicobacter*
Humans
Methylation
Stomach Neoplasms

Figure

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  Fig. 1. Changes in quantitative value of MethyLight assay (percentage of methylated reference, PMR) of p16, RUNX-3 and CDH1 at baseline and after one year in the Helicobacter pylori eradication group. PMR value in p16 and CDH1 were significantly reduced one year after eradication.

Reference

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