title: 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.
authors.affiliation: 1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2. Department of Anaesthesiology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hon-Kit
authors.initials: HK
authors.lastname: Lau
authors.affiliation: 1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3. Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan; 4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: 1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 5. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: 1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 6. Department of Beauty Science, National Taichung University of Science and Technology, Taichung, Taiwan.
authors.forename: Hsiang-Ling
authors.initials: HL
authors.lastname: Wang
authors.affiliation: 7. Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: Wu-Hsien
authors.initials: WH
authors.lastname: Kuo
authors.affiliation: 1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8. Deptartment of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Chao-Bin
authors.initials: CB
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: C000589760:IL18 protein, human; D020382:Interleukin-18; D000509:alpha-Fetoproteins
keywords: hepatitis B virus; hepatocellular carcinoma; interleukin-18