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.
Moriichi
Kentaro
K
Department of Medicine, Division of Gastroenterology and Hematology/Oncology, Asahikawa Medical College, Asahikawa, Japan.
Watari
Jiro
J
Das
Kiron M
KM
Tanabe
Hiroki
H
Fujiya
Mikihiro
M
Ashida
Toshifumi
T
Kohgo
Yutaka
Y
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000235:genetics; D018899:CpG Islands; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D019175:DNA Methylation; D017931:DNA Primers; D004260:DNA Repair; D005260:Female; D017491:Genes, APC; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D007564:Japan; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D017931:DNA Primers; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D004247:DNA; D000070957:MutL Protein Homolog 1