Association between Interleukin-18 Polymorphisms and Hepatocellular Carcinoma Occurrence and Clinical Progression

Abstract

We investigated the association between interleukin-18 (IL-18) polymorphisms and the susceptibility and clinicopathological state of hepatocellular carcinoma (HCC). In total, 901 participants, including 559 healthy controls and 342 patients with HCC, were recruited. The allelic discrimination of -607A/C (rs1946518) and -137G/C (rs187238) polymorphisms of IL-18 was assessed through real-time polymerase chain reaction by performing the TaqMan assay. The IL-18 -137G/C polymorphism but not the -607A/C polymorphism showed a significant association with the risk of HCC. Participants carrying the IL-18 -137 polymorphism with heterozygous G/C and homozygous CC genotypes showed a 1.987-fold increase (95% CI = 1.301-3.032; p = 0.001) in the risk of HCC compared with those homozygous for wild-type G/G. The 342 patients with HCC carrying the IL-18 -137G/C polymorphism were positive for hepatitis B virus (HBV) infection with an adjusted odds ratio of 1.668. Moreover, the 142 HBV positive patients with HCC and the IL-18 -137 polymorphism were positive for at least one C genotype and showed significant vascular invasion (p = 0.018). Furthermore, the level of α-fetoprotein was high in the patients carrying the IL-18 -137 polymorphism with GC+CC alleles (p = 0.011). In conclusion, the IL-18 -137G/C polymorphism with a GC+CC genotype could be a factor that increases the risk of HCC. Furthermore, the correlation between the IL-18 -137G/C polymorphism and HCC-related HBV infection is a risk factor for vascular invasion and has a synergistic effect that can further enhance HCC prognosis.