Virulence of infecting helicobacter pylori strains and intensity of mononuclear cell infiltration are associated with levels of DNA hypermethylation in gastric mucosae

Barbara G. Schneider, M. Blanca Piazuelo, Liviu A. Sicinschi, Robertino Mera, Dun Fa Peng, Juan Carlos Roa, Judith Romero-Gallo, Alberto G. Delgado, Thibaut de Sablet, Luis E. Bravo, Keith T. Wilson, Wael El-Rifai, Richard M. Peek, Pelayo Correa

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Abstract

DNA methylation changes are known to occur in gastric cancers and in premalignant lesions of the gastric muco-sae. In order to examine variables associated with methylation levels, we quantitatively evaluated DNA methylation in tumors, non-tumor gastric mucosae, and in gastric biopsies at promoters of 5 genes with methylation alterations that discriminate gastric cancers from non-tumor epithelia (E N1, P C D H10, RSP O2, Z I C1, and Z N F 61 0). among colombian subjects at high and low risk for gastric cancer, biopsies from subjects from the high-risk region had significantly higher levels of methylation at these 5 genes than samples from subjects in the low risk region (P ≤ 0.003). When results were stratified by Helicobacter pylori infection status, infection with a cagA positive, vacA s1m1 strain was significantly associated with highest methylat ion levels, compared with other strains (P = 0.024 to 0.001). More severe gastric inflammation and more advanced precancerous lesions were also associated with higher levels of DNA methylation (P ≤ 0.001). In a multivariate model, location of residence of the subject and the presence of cagA and vacA s1m1 in the H. pylori strain were independent variables associated with higher methylation in all 5 genes. High levels of mononuclear cell infiltration were significantly related to methylation in PCDH10, RSPO2, and ZI C1 genes. These results indicate that for these genes, levels of methylation in precancerous lesions are related to H. pylori virulence, geographic region and measures of chronic inflammation. These genes seem predisposed to sustain significant quantitative changes in DNA methylation at early stages of the gastric precancerous process.

Original languageEnglish (US)
Pages (from-to)1153-1161
Number of pages9
JournalEpigenetics
Volume8
Issue number11
DOIs
StatePublished - Jan 1 2013

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Keywords

  • Biopsy
  • Chronic inflammation
  • Gastric cancer
  • Helicobacter
  • Methylation
  • Pyrosequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Schneider, B. G., Blanca Piazuelo, M., Sicinschi, L. A., Mera, R., Peng, D. F., Roa, J. C., Romero-Gallo, J., Delgado, A. G., de Sablet, T., Bravo, L. E., Wilson, K. T., El-Rifai, W., Peek, R. M., & Correa, P. (2013). Virulence of infecting helicobacter pylori strains and intensity of mononuclear cell infiltration are associated with levels of DNA hypermethylation in gastric mucosae. Epigenetics, 8(11), 1153-1161. https://doi.org/10.4161/epi.26072