Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population

Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori ( H. pylori ) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE ( n = 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE ( n = 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1 , E‐cadherin , p16 and APC , and immunoreactivity using a monoclonal antibody (mAb) Das‐1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E‐cadherin and APC , and mAb Das‐1 reactivity in Group BE was significantly higher than that in Group CLE ( p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E‐cadherin methylation and mAb Das‐1 reactivity showed a significantly higher incidence in patients with H.pylori infection than in those without H. pylori infection ( p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E‐cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das‐1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population. © 2008 Wiley‐Liss, Inc.