Global DNA Methylation and Tumor Suppressor Gene Promoter Methylation and Gastric Cancer Risk in an Omani Arab Population

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.

KEYWORDS::

• DNA methylation
• epigenetics
• gastric carcinoma
• Oman
• tumor suppressor genes

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.