Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer.
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.
Schneider
Barbara G
BG
Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0252, USA. barbara.schneider@vanderbilt.edu
Peng
Dun-Fa
DF
Camargo
M Constanza
MC
Piazuelo
M Blanca
MB
Sicinschi
Liviu A
LA
Mera
Robertino
R
Romero-Gallo
Judith
J
Delgado
Alberto G
AG
Bravo
Luis E
LE
Wilson
Keith T
KT
Peek
Richard M
RM
Correa
Pelayo
P
El-Rifai
Wael
W
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
D018797:Cell Cycle Proteins; D006023:Glycoproteins; D009687:Nuclear Proteins; C412566:RPRM protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1