Association Between Polymorphisms of Interleukin 1 Family Genes and Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies occurring worldwide and is most frequent type of liver cancer. The risk for developing HCC increases with the severity of inflammation and fibrosis. The members of the interleukin-1 (IL-1) family are primarily proinflammatory cytokines due to their ability to stimulate the expression of genes associated with inflammation and autoimmune diseases. Several studies have suggested that some proinflammatory cytokines, such as the IL-1 family (IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist) are involved in the pathogenesis of HCC. Material/Methods: This study aimed to determine whether polymorphisms in the IL-1 family of genes are associated with HCC. We analyzed 178 HCC patients and 397 controls to investigate the association between polymorphisms in IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist (IL-1RA) genes and HCC in the Korean population. All subjects were genotyped for the selected SNPs in IL-1 alpha, IL-1 beta, and IL-1RA genes by Golden-Gate SNP Genotyping Assay. Results: Statistical analysis revealed a significant association at IL-1 beta between HCC and controls. Three individual polymorphisms (rs1143633, rs3917356, and rs1143627) were found to be associated with HCC. The SNPs of IL-1 beta gene (rs1143633A>G and rs1143627T>C) protected against HCC in the dominant model (p=0.027, OR=0.59, 95% CI=0.37-0.94; p=0.019, OR=0.56, 95% CI=0.34-0.91). The SNP of IL-1 beta gene (rs3917356G>A) increased the risk of HCC in the recessive model (p<0.001, OR=2.58, 95% CI=1.53-4.33), whereas other SNPs in IL-1 alpha and IL-1RA showed no significant association between HCC patients and controls. Conclusions: These results suggest that IL-1 beta in the IL-1 family contributes to HCC susceptibility.