title: The accumulation of DNA demethylation in Sat α in normal gastric tissues             with Helicobacter pylori infection renders susceptibility to gastric cancer in             some individuals.
abstract: Helicobacter pylori (HP) infection is widely recognized as a risk factor             for gastric cancer, but only a minority of infected individuals develop gastric             cancer. The aim of this study was to determine whether DNA demethylation in non-cancerous             gastric mucosa (NGM) significantly enhances susceptibility to gastric cancer.             A total of 165 healthy volunteers, including 83 HP-positive and 82-negative individuals,             as well as 83 patients with single and 18 with synchronous double gastric cancer             (GC) were enrolled in this study. The relative demethylation levels (RDLs) of             repetitive sequences, including Alu, LINE-1 and Sat α, were quantified by real-time             methylation-specific polymerase chain reaction. The Alu RDL did not exhibit any             differences within each respective group, whereas LINE-1 RDL was significantly             elevated in cancer tissues compared with the NGM in the other groups (P<0.001).             Our results indicated that a gradual increase in Sat α RDL correlated with HP             infection and cancer development. Sat α RDL was significantly elevated in the             NGM in HP-positive compared with HP-negative (P<0.001), and significantly elevated             in cancer tissues (P<0.001). Although the Sat α RDL of the NGM in the total             population increased in an age-dependent manner, it was significantly increased             in a fraction of younger GC patients (<45 years) compared with all of the others             (45 years or older, P=0.0391). In addition, double GC exhibited a significantly             higher Sat α RDL in the NGM compared with single GC (P=0.0014). In these two fractions,             Sat α RDL in the NGM exhibited an inverse correlation with age. In conclusion,             the present study demonstrated that the accumulation of DNA demethylation in Sat             α RDL in the NGM with HP infection potentially renders susceptibility to gastric             cancer in a fraction of GC patients younger than 45 years or in patients with             multiple cancers.
authors.affiliation: Department of Surgery, Saitama Medical Center, Jichi Medical                     University, Saitama 330-8503, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Saito
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Maeda
authors.forename: Takaharu
authors.initials: T
authors.lastname: Kato
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kamiyama
authors.forename: Kei
authors.initials: K
authors.lastname: Koizumi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miyaki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kiyozaki
authors.forename: Fumio
authors.initials: F
authors.lastname: Konishi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D020087:Alu Elements; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D013270:Stomach / Q000382:microbiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology*
chemical_list: D004276:DNA, Satellite