Novel interleukin 1β polymorphism increased the risk of gastric cancer in a Korean population

Abstract

BACKGROUND: Polymorphisms in the gene for interleukin 1beta (IL-1B) have been found to increase the risks of gastric cancer and its precursors in response to Helicobacter pylori infection in white populations. however, there has been no independent confirmation of the role of IL-1B markers in gastric cancer patients from Asian populations. Moreover, there have been conflicting data regarding the effect of IL-1B-511/-31 on the risk of gastric cancer or its precursors in Asian populations. Therefore, we assessed an additional polymorphism in the promoter region of IL-1B at position-1473 with the IL-1B-511/-31 polymorphisms in a Korean population. METHODS: In a case-control study, including 331 gastric cancer cases and 433 controls, we assessed the association between the three polymorphisms and the risk of gastric cancer. All genotyping was performed in duplicate. To assess the DNA-binding activity of IL-1B-1473 in vitro, we performed an electrophoretic mobility shift assay (EMSA). RESULTS: When cases were divided according to the histologic type of the tumor, a significant difference in genotype frequencies for IL-1B-1473 was observed only between intestinal-type cases and controls (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.5 and OR 2.1 and 95% CI, 1.1-4.2 in the CG and GG genotypes, respectively). In the cases, there was a deviation from Hardy-Weinberg equilibrium in the IL-1B-511/-31 loci confined to the intestinal type, due to the excess of heterozygotes. The IL-1B-1473G allele showed decreased binding to nuclear extract, indicating a wearker promoter activity on EMSA. CONCLUSIONS: We identified a novel single-nucleotide polymorphism, 1473C-->G, in the IL-1B promoter that was significantly associated with gastric cancer among Koreans. Our results also suggest that the association between IL-1B polymorphism and an increased risk of gastric cancer may depend on the histologic type of gastric cancer.