Keith Wilson
Faculty Member
Last active: 12/19/2020

Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer.

Schneider BG, Peng DF, Camargo MC, Piazuelo MB, Sicinschi LA, Mera R, Romero-Gallo J, Delgado AG, Bravo LE, Wilson KT, Peek RM, Correa P, El-Rifai W
Int J Cancer. 2010 127 (11): 2588-97

PMID: 20178103 · PMCID: PMC2916942 · DOI:10.1002/ijc.25274

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.

MeSH Terms (16)

Adult Biopsy Cell Cycle Proteins DNA Methylation Genetic Predisposition to Disease Glycoproteins Helicobacter Infections Helicobacter pylori Humans Male Middle Aged Nuclear Proteins Promoter Regions, Genetic Risk Factors Stomach Neoplasms Twist-Related Protein 1

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