title: Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer.
abstract: Gene promoter CpG island hypermethylation is associated with Helicobacter pylori (H. pylori) infection and may be an important initiator of gastric carcinogenesis. To examine factors influencing methylation, we utilized bisulfite Pyrosequencing® technology for quantitative analysis of promoter DNA methylation in RPRM, APC, MGMT and TWIST1 genes using DNA from 86 gastric biopsies from Colombian residents of areas with high and low incidence of gastric cancer. H. pylori colonies were cultured from the same subjects, and gastric pathology was evaluated. Virulence factors cagA (including segments of the 3' end, encoding EPIYA polymorphisms) and vacA s and m regions were characterized in the H. pylori strains. Using univariate analysis, we found significantly elevated levels of RPRM and TWIST1 promoter DNA methylation in biopsies from residents of the high-risk region compared to those from residents of the low-risk region. The presence of cagA and vacA s1m1 alleles were independently associated with elevated levels of promoter DNA methylation of RPRM and MGMT. Using multivariate analysis, DNA methylation of RPRM was associated with location of residence, cagA and vacA s1m1 status and methylation of TWIST1. We conclude that cagA and vacA virulence determinants are significantly associated with quantitative differences in promoter DNA methylation in these populations, but that other as yet undefined factors that differ between the populations may also contribute to variation in methylation status.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0252, USA. barbara.schneider@vanderbilt.edu
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Schneider
authors.forename: Dun-Fa
authors.initials: DF
authors.lastname: Peng
authors.forename: M Constanza
authors.initials: MC
authors.lastname: Camargo
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.forename: Liviu A
authors.initials: LA
authors.lastname: Sicinschi
authors.forename: Robertino
authors.initials: R
authors.lastname: Mera
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Delgado
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bravo
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
mesh_terms: D000328:Adult; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000235:genetics; D019175:DNA Methylation; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D051879:Twist-Related Protein 1 / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D006023:Glycoproteins; D009687:Nuclear Proteins; C412566:RPRM protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1