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

Barbara G. Schneider, Dunfa Peng, M. Constanza Camargo, M. Blanca Piazuelo, Liviu A. Sicinschi, Robertino Mera, Judith Romero-Gallo, Alberto G. Delgado, Luis E. Bravo, Keith T. Wilson, Richard M. Peek, Pelayo Correa, Wael El-Rifai

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2588-2597
Number of pages10
JournalInternational Journal of Cancer
Volume127
Issue number11
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

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DNA Methylation
Stomach Neoplasms
Stomach
Biopsy
Helicobacter pylori
DNA
Methylation
CpG Islands
Helicobacter Infections
Virulence Factors
Population
Genes
Virulence
Carcinogenesis
Multivariate Analysis
Alleles
Pathology
Technology
Incidence

Keywords

  • Colombia
  • epigenetics
  • Helicobacter
  • intestinal metaplasia
  • premalignant
  • promoter
  • Pyrosequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. / Schneider, Barbara G.; Peng, Dunfa; Camargo, M. Constanza; Piazuelo, M. Blanca; Sicinschi, Liviu A.; Mera, Robertino; Romero-Gallo, Judith; Delgado, Alberto G.; Bravo, Luis E.; Wilson, Keith T.; Peek, Richard M.; Correa, Pelayo; El-Rifai, Wael.

In: International Journal of Cancer, Vol. 127, No. 11, 01.12.2010, p. 2588-2597.

Research output: Contribution to journalArticle

Schneider, BG, Peng, D, Camargo, MC, Piazuelo, MB, Sicinschi, LA, Mera, R, Romero-Gallo, J, Delgado, AG, Bravo, LE, Wilson, KT, Peek, RM, Correa, P & El-Rifai, W 2010, 'Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer', International Journal of Cancer, vol. 127, no. 11, pp. 2588-2597. https://doi.org/10.1002/ijc.25274
Schneider, Barbara G. ; Peng, Dunfa ; Camargo, M. Constanza ; Piazuelo, M. Blanca ; Sicinschi, Liviu A. ; Mera, Robertino ; Romero-Gallo, Judith ; Delgado, Alberto G. ; Bravo, Luis E. ; Wilson, Keith T. ; Peek, Richard M. ; Correa, Pelayo ; El-Rifai, Wael. / Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. In: International Journal of Cancer. 2010 ; Vol. 127, No. 11. pp. 2588-2597.
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AU - Sicinschi, Liviu A.

AU - Mera, Robertino

AU - Romero-Gallo, Judith

AU - Delgado, Alberto G.

AU - Bravo, Luis E.

AU - Wilson, Keith T.

AU - Peek, Richard M.

AU - Correa, Pelayo

AU - El-Rifai, Wael

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