title: Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers.
abstract: BACKGROUND
  Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori-negative cases with a gastric cancer had higher methylation levels than those of H. pylori-negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers.
  
  
  METHODS
  Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands.
  
  
  RESULTS
  In H. pylori-negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P < 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori-positive individuals were increased to various degrees in all the three groups.
  
  
  CONCLUSIONS
  In H. pylori-negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers.
authors.affiliation: Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Ichiro
authors.initials: I
authors.lastname: Oda
authors.forename: Takuji
authors.initials: T
authors.lastname: Gotoda
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Daizo
authors.initials: D
authors.lastname: Saito
mesh_terms: D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D005838:Genotype; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D013274:Stomach Neoplasms / Q000473:pathology*