Global DNA methylation and tumor suppressor gene promoter methylation and gastric cancer risk in an Omani Arab population

Epigenomics. 2011 Aug;3(4):417-29. doi: 10.2217/epi.11.65.

Abstract

Aim: We carried out a case-control study in an Omani Arab population to investigate the association between gastric cancer and peripheral blood leukocyte DNA methylation in LINE-1 and in the tumor suppressor genes CDH1, p16, TP53 and RUNX3.

Materials & methods: We quantified methylation (%5-mC) in DNA extracted from peripheral blood leukocytes via pyrosequencing. We calculated odds ratios (ORs) and 95% CIs using logistic regression.

Results: We found patterns of global hypomethylation (LINE-1: OR(continuous) = 0.59; 95% CI: 0.42-0.82) and TP53 promoter hypomethylation (OR(continuous) = 0.64; 95% CI: 0.16-0.85) for cases versus controls; p16 promoter region hypomethylation was not statistically significant. Evaluating LINE-1, TP53 and p16 jointly yielded a more pronounced negative association with gastric cancer (OR: 0.24; 95% CI: 0.09-0.66). Age was a significant effect modifier. We found no differences by tumor grade, stage or histology.

Conclusion: We found a pattern of global hypomethylation and promoter region hypomethylation of TP53 and p16 in cases versus controls for this population of Omani Arabs.

MeSH terms

  • Antigens, CD
  • Arabs / genetics
  • Cadherins / physiology
  • Case-Control Studies
  • Core Binding Factor Alpha 3 Subunit / physiology
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Methylation / physiology*
  • Genes, Tumor Suppressor*
  • Humans
  • Leukocytes / metabolism
  • Logistic Models
  • Long Interspersed Nucleotide Elements / physiology*
  • Neoplasm Proteins / physiology
  • Odds Ratio
  • Oman
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / physiology*
  • Risk Assessment
  • Sequence Analysis, DNA / methods
  • Stomach Neoplasms / metabolism*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CDKN2A protein, human
  • Cadherins
  • Core Binding Factor Alpha 3 Subunit
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • Runx3 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53