Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication.
BACKGROUND
Helicobacter pylori (HP) infection potently induces aberrant DNA methylation in gastric mucosae, and its accumulation is associated with gastric cancer risk. Cross-sectional analysis of methylation levels (fraction of methylated DNA molecules) and temporal analysis of methylation incidence suggested that methylation levels decrease after HP infection discontinues. We aimed to demonstrate the decrease in methylation levels.


METHODS
Thirty-five patients with HP infection who had undergone curative endoscopic resection and 11 healthy volunteers were recruited. Methylation levels were quantified by real-time methylation-specific PCR. Histology was evaluated according to the updated Sydney System.


RESULTS
In the 20 patients with successful eradication, the FLNc methylation level, along with infiltration of inflammatory cells, decreased from 0.6 to 0.4% at 6 weeks (P = 0.049) and remained low at 1 year. The THBD methylation level (30.1%) remained high at 6 weeks, but decreased to 19.0% at 1 year (P = 0.0032). Nine healthy volunteers with successful eradication tended to show a decrease of both FLNc and THBD at 6 weeks. However, the methylation levels after the decrease were still higher than those of healthy individuals without HP infection. In the 15 patients with persistent infection, the methylation levels remained the same. Before eradication, the THBD methylation level correlated with the degree of inflammatory cell infiltration (P < 0.05).


CONCLUSIONS
Methylation levels in gastric mucosae decreased to certain levels after HP eradication in profiles unique to individual markers. Involvement of chronic inflammation in methylation induction was suggested.
Nakajima
Takeshi
T
Carcinogenesis Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. tnakajim@ncc.go.jp
Enomoto
Shotaro
S
Yamashita
Satoshi
S
Ando
Takayuki
T
Nakanishi
Yukihiro
Y
Nakazawa
Kazuyuki
K
Oda
Ichiro
I
Gotoda
Takuji
T
Ushijima
Toshikazu
T
D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology / Q000601:surgery; D013997:Time Factors