Infectious Causes of Cancer

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

  1. Barbara G. Schneider1,†,*,
  2. Dun-Fa Peng2,
  3. M. Constanza Camargo3,
  4. M. Blanca Piazuelo1,
  5. Liviu A. Sicinschi1,
  6. Robertino Mera1,
  7. Judith Romero-Gallo1,
  8. Alberto G. Delgado1,
  9. Luis E. Bravo4,
  10. Keith T. Wilson1,5,
  11. Richard M. Peek Jr.1,
  12. Pelayo Correa1,
  13. Wael El-Rifai2

Article first published online: 22 FEB 2010

DOI: 10.1002/ijc.25274

Issue

International Journal of Cancer

International Journal of Cancer

Volume 127, Issue 11, pages 2588–2597, 1 December 2010

Additional Information

How to Cite

Schneider, B. G., Peng, D.-F., Camargo, M. C., Piazuelo, M. B., Sicinschi, L. A., Mera, R., Romero-Gallo, J., Delgado, A. G., Bravo, L. E., Wilson, K. T., Peek, R. M., Correa, P. and El-Rifai, W. (2010), Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. Int. J. Cancer, 127: 2588–2597. doi: 10.1002/ijc.25274

Author Information

  1. 1

    Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN

  2. 2

    Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN

  3. 3

    Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL

  4. 4

    Department of Pathology, School of Medicine, Universidad del Valle, Cali, Colombia

  5. 5

    Department of Veterans Affairs, Veterans Affairs Tennessee Valley Healthcare System and Office of Medical Research, Nashville, TN

  1. †

    Tel.: 615-343-3959, Fax: 615-343-6229

*2215 Garland Ave., Room 1030C, MRB IV, Nashville, TN 37232-0252; USA

  1. †

    Tel.: 615-343-3959, Fax: 615-343-6229

Publication History

  1. Issue published online: 22 FEB 2010
  2. Article first published online: 22 FEB 2010
  3. Manuscript Accepted: 8 FEB 2010
  4. Manuscript Received: 22 OCT 2009

Funded by

  • NCRR/NIH (CTSA). Grant Number: 1 UL1 RR024975
  • National Cancer Institute. Grant Numbers: P01 CA028842, R01 CA095103, R01 CA077955, R01 CA093999, P01 CA116087, P30DK058404, R01 DK053620, DK058587

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Keywords:

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

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.

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