Association between IL-18 polymorphisms, serum levels, and HBV-related hepatocellular carcinoma in a Chinese population: a retrospective case-control study

Background: Interleukin (IL)-18 gene polymorphisms have been found to play multiple roles in various diseases. However, studies focused on its involvement in hepatocellular carcinoma (HCC) remains controversial, and no much study has taken IL-18 serum levels into consideration. This study investigates the association between IL-18 polymorphisms and risk of hepatitis B virus-related HCC and their impact on serum IL-18 serum levels. Methods: A total of 153 patients and 165 healthy controls were enrolled in this study. Polymorphisms at positions -607C/A and -137G/C in the IL-18 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Serum IL-18 levels were determined with an ELISA kit. Results: No relationship was found between the -607C/A polymorphism and an individual's susceptibility to HCC. For the -137G/C polymorphism, the GC genotype and C allele were found to be significantly associated with decreased HCC risk (OR 0.506, 95% CI 0.290-0.882, P = 0.016 and OR 0.520, 95% CI 0.332-0.814, P = 0.004, respectively). The A-607C-137 haplotype was also associated with a significant decreased risk of HCC (OR 0.495, 95% CI 0.294-0.834, P = 0.007). Serum IL-18 levels were found to be significantly lower in HCC patients compared to the control group in both the overall population and subjects with the different SNPs. Further, no association was found between serum IL-18 levels and the different genotypes within the same SNP. Conclusion: These findings suggest that the -137G/C SNP in IL-18 may be a protective factor against HCC. Nevertheless, none of the studied SNPs was associated with the expression of IL-18.