ICAM-1基因多型性對肝癌的易感性和臨床病理之研究

Association of Intercellular Adhesion Molecule 1 Polymorphisms on Hepatocellular Carcinoma Susceptibility

陳聰波(Tsung-Po Chen)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/博士(2016年)

摘要

Intercellular Adhesion Molecule-1 (ICAM-1)是一種醣基化修飾的穿膜蛋白，主要表現在內皮細胞和免疫細胞。已知與肝癌細胞的生長、侵襲和轉移有關。但ICAM-1的基因多型性和肝癌成因的相關性則未有研究。本研究是以ICAM-1的單核苷酸多型性 (Single-nucleotide polymorphism, SNP) 對肝癌易感性及臨床病理特性之影響所做的分析。在總數為918的臨床檢體中，包含613位非肝癌控制組與305位肝癌病患分別利用即時定量聚合酶連鎖反應來分析ICAM-1的單核苷酸多型性 rs3093030、rs5491、 rs281432和 rs5498。在進行年齡、性別、喝酒習慣和抽菸狀態的分類後顯示在rs5498的多型性中帶有G (A/G或G/G)的基因型並且有抽菸習慣的人較帶AA基因且無抽菸習慣的人有1.713倍的風險罹患肝癌(adjusted odds ratio [AOR]: 1.713; 95% confidence interval [CI]: 1.091-2.690; p=0.036)。然而，比對其他因子後發現rs5498基因多型性帶有較低的血管侵襲能力(AOR: 0.309; 95% CI, 0.103-0.926; p =0.036)。此研究顯示，在有吸煙習慣的人，ICAM-1基因的rs5498基因多型性若為A/G或G/G則罹患肝癌的機率是正常基因型的1.7倍。因此，ICAM-1 的rs5498基因多型性與環境因子的相互作用可能改變對肝癌的易感性。除此之外，ICAM-1 rs5498亦可作預測吸煙者HCC患者的血管侵襲風險的標記。

關鍵字

細胞問黏附分子-1 ； 肝癌 ； 基因多型性

並列摘要

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.

並列關鍵字

ICAM-1 ； hepatocellular carcinoma ； polymorphisms

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