The association between interleukin 1 beta polymorphism and hypermethylation at tumor suppressor genes in gastric cancer

Abstract

Background: The importance of interleukin 1beta polymorphism (IL-1) has been demonstrated in gastric cancer through the production of hypochlorhydria and atrophic gastritis. Hypermethylation at tumor suppressor gene is an important mechanism in gastric carcinogenesis. Aim: to examine if association exists between IL-1 polymorphism and hypermethylation. Methods: We determined IL-1B-511/-31 and IL-1RN genotypes in 41 patients with gastric cancer. Hypermethylation at MGMT and p16 were assessed in these patients using Methylation Specific PCR and confirmed by sequencing. Results: Within the IL-1B gene, the T and C alleles at the -511 locus were in near total linkage disequilibrium with the C and T alleles at the -31 locus. The allele frequencies at IL-1B-511 was 8/41 (19.5%), 28/41 (68.3%), and 5/41 (12.2%) for T/T, C/T, and C/C genotypes, respectively. Allele 2 of the IL-1RN locus was not detected in any patients. Frequency of hypermethylation at MGMT and p16 was 31.7% (13/41) and 29.3% (12/41), respectively. The presence of hypermethylation at any locus was observed in 6/8 (75%) patients with the proinflammatory IL-1B-511 T/T genotype, in comparison to 1/5 (20%) of the patients with IL-1B-511 C/C genotype (p 0.04), and in 16/28 (57%) of the patients with IL-1B-511 T/C genotype. Conclusion: Proinflammatory IL-1 polymorphisms are associated with hypermethylation at tumor suppressor genes in gastric cancer, which may be the result of hypochlorhydria and atrophic gastritis.