Interleukin Polymorphisms and Differential Methylation Status in Gastric Cancer: An Association with Helicobacter Pylori Infection

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.

KEYWORDS::

• gastric cancer
• Helicobacter pylori
• interleukin polymorphisms
• methylation
• virulence genes

Financial & competing interests disclosure

This work was supported by CNPq–Conselho Nacional de Desenvolvimento Científico e Tecnológico (BRAZIL), grant number 480554/2008. The authors have no other 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 apart from those disclosed.

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.

Additional information

Funding

This work was supported by CNPq–Conselho Nacional de Desenvolvimento Científico e Tecnológico (BRAZIL), grant number 480554/2008. The authors have no other 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 apart from those disclosed.