Interleukin polymorphisms and differential methylation status in gastric cancer: an association with Helicobacter pylori infection

Epigenomics. 2013 Apr;5(2):167-75. doi: 10.2217/epi.13.7.

Abstract

Aim: Interleukin polymorphisms and Helicobacter pylori infection are believed to play critical roles in DNA methylation, a process frequently associated with carcinogenesis. The aim of this study was to determine the associations between interleukin polymorphisms and methylation status of three genes related to gastric cancer. Furthermore, the influence of the H. pylori strains was evaluated.

Materials & methods: 75 gastric tumor samples had the DNA extracted for interleukin polymorphisms genotyping by PCR-RFLP, promoter methylation by MS-PCR and detection and subtyping of H. pylori by PCR.

Results: In the cardia tumors, methylation in the COX-2 promoter was associated with IL1RN*2 (p = 0.015), and the associated genotypes IL1B511T + IL1RN*2 seem to be important in the methylation of COX-2 (p = 0.013), especially in the presence of cagA(+) (p = 0.026) and vacAs1 (p = 0.025) H. pylori strains. The associated genotypes IL6 CC+TNF GG seem to be involved in the unmethylation of CDKN2A (p = 0.046), along with H. pylori cagA(+) infection.

Conclusion: DNA methylation in gastric cancer seems to be influenced by the presence of interleukin polymorphisms and by the H. pylori cagA/vacAs1m1 strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bacterial Proteins / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclooxygenase 2 / genetics*
  • DNA Methylation / genetics*
  • Epigenesis, Genetic / genetics
  • Female
  • Genetic Association Studies
  • Helicobacter Infections / complications
  • Helicobacter Infections / genetics
  • Helicobacter pylori / genetics
  • Helicobacter pylori / pathogenicity
  • Humans
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology

Substances

  • Bacterial Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • IL6 protein, human
  • Interleukin-6
  • Cyclooxygenase 2
  • PTGS2 protein, human