1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
2. Department of Anaesthesiology, Chung Shan Medical University Hospital, Taichung, Taiwan
3. Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan
4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
5. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
6. Department of Beauty Science, National Taichung University of Science and Technology, Taichung, Taiwan
7. Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
8. Deptartment of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
9. Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
10. Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
# These authors contributed equally to the work.
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.
Keywords: hepatocellular carcinoma, interleukin-18, hepatitis B virus