Chen Tsung-Po, Lee Hsiang-Lin, Huang Yu-Hui, Hsieh Ming-Ju, Chiang Whei-Ling, Kuo Wu-Hsien, Chou Ming-Chih, Yang Shun-Fa, Yeh Chao-Bin
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
Tumour Biol. 2016 Feb;37(2):2067-74. doi: 10.1007/s13277-015-3992-z. Epub 2015 Sep 5.
Intercellular adhesion molecule-1 (ICAM-1) is a human protein encoded by the ICAM-1 gene and is typically expressed on endothelial cells and immune cells. ICAM-1 is associated with episode, growth, invasion, and metastasis of hepatocellular carcinoma (HCC). However, the association between ICAM-1 genetic variants and the risk of HCC is undetermined. In this study, we investigated the potential associations of ICAM-1 single nucleotide polymorphisms (SNPs) with susceptibility to HCC and its clinicopathological characteristics. A total of 918 participants, including 613 controls participants and 305 patients with HCC, were selected for the analysis of ICAM-1 SNPs (rs3093030, rs5491, rs281432, and rs5498) by using real-time PCR genotyping. After adjusting for covariants of age, sex, and alcohol consumption, 125 smoker patients with HCC carrying at least one G genotype (AG and GG) in rs5498 were observed to have a higher HCC risk compared with 231 smoker control participants carrying the wild-type allele AA (adjusted odds ratio (AOR), 1.713; 95 % confidence interval (CI), 1.091-2.690; P = 0.019). However, patients who possess at least one polymorphic allele of rs5498 are less prone to develop vascular invasive (AOR, 0.309; 95 % CI, 0.103-0.926; P = 0.036). The results suggest that the genetic polymorphism in ICAM-1 rs5498 SNPs with genotype AG and GG is associated with HCC risk among smokers. Moreover, gene and environment interactions of ICAM-1 rs5498 polymorphisms might alter susceptibility to liver cancer. Therefore, ICAM-1 rs5498 may serve as a marker to predict the vascular invasion risk in smoker patients with HCC.
细胞间黏附分子-1(ICAM-1)是一种由ICAM-1基因编码的人类蛋白质,通常在内皮细胞和免疫细胞上表达。ICAM-1与肝细胞癌(HCC)的发作、生长、侵袭和转移有关。然而,ICAM-1基因变异与HCC风险之间的关联尚未确定。在本研究中,我们调查了ICAM-1单核苷酸多态性(SNP)与HCC易感性及其临床病理特征之间的潜在关联。通过实时PCR基因分型,共选择了918名参与者,包括613名对照参与者和305名HCC患者,用于分析ICAM-1 SNP(rs3093030、rs5491、rs281432和rs5498)。在调整年龄、性别和饮酒等协变量后,观察到125名携带rs5498中至少一个G基因型(AG和GG)的吸烟HCC患者与231名携带野生型等位基因AA的吸烟对照参与者相比,HCC风险更高(调整后的优势比(AOR)为1.713;95%置信区间(CI)为1.091-2.690;P = 0.019)。然而,拥有rs5498至少一个多态性等位基因的患者发生血管侵袭的可能性较小(AOR为0.309;95%CI为0.103-0.926;P = 0.036)。结果表明,ICAM-1 rs5498 SNP中基因型为AG和GG的基因多态性与吸烟者的HCC风险相关。此外,ICAM-1 rs5498多态性的基因与环境相互作用可能会改变对肝癌的易感性。因此,ICAM-1 rs5498可作为预测吸烟HCC患者血管侵袭风险的标志物。