Lau Hon-Kit, Hsieh Ming-Ju, Yang Shun-Fa, Wang Hsiang-Ling, Kuo Wu-Hsien, Lee Hsiang-Lin, Yeh Chao-Bin
1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2. Department of Anaesthesiology, Chung Shan Medical University Hospital, Taichung, Taiwan.
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.
Int J Med Sci. 2016 Jul 5;13(7):556-61. doi: 10.7150/ijms.15853. eCollection 2016.
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.
我们研究了白细胞介素-18（IL-18）基因多态性与肝细胞癌（HCC）易感性及临床病理状态之间的关联。共招募了901名参与者，包括559名健康对照者和342名HCC患者。通过实时聚合酶链反应，采用TaqMan分析法评估IL-18基因-607A/C（rs1946518）和-137G/C（rs187238）多态性的等位基因鉴别情况。结果显示，IL-18基因-137G/C多态性而非-607A/C多态性与HCC风险显著相关。与野生型G/G纯合子相比，携带IL-18基因-137多态性杂合子G/C和纯合子CC基因型的参与者患HCC的风险增加了1.987倍（95%置信区间=1.301-3.032；p=0.001）。携带IL-18基因-137G/C多态性的342例HCC患者中，乙肝病毒（HBV）感染呈阳性，校正比值比为1.668。此外，142例HBV阳性的HCC患者且具有IL-18基因-137多态性，至少有一种C基因型呈阳性，且显示出显著的血管侵犯（p=0.018）。此外，携带IL-18基因-137多态性且具有GC+CC等位基因的患者甲胎蛋白水平较高（p=0.011）。总之，具有GC+CC基因型的IL-18基因-137G/C多态性可能是增加HCC风险的一个因素。此外，IL-18基因-137G/C多态性与HCC相关HBV感染之间的相关性是血管侵犯的一个危险因素，并且具有协同作用，可进一步加重HCC的预后。
