title: Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae.
abstract: The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori (H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues (P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals (P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection (P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients (P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosumi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Kazuto
authors.initials: K
authors.lastname: Harada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyake
authors.forename: Daisuke
authors.initials: D
authors.lastname: Izumi
authors.forename: Ryuma
authors.initials: R
authors.lastname: Tokunaga
authors.forename: Asuka
authors.initials: A
authors.lastname: Murata
authors.forename: Kojiro
authors.initials: K
authors.lastname: Eto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sugihara
authors.forename: Hironobu
authors.initials: H
authors.lastname: Shigaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Iwagami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Naoya
authors.initials: N
authors.lastname: Yoshida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D016480:Helicobacter pylori; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology