Sheu Ming-Jen, Hsieh Ming-Ju, Chiang Whei-Ling, Yang Shun-Fa, Lee Hsiang-Lin, Lee Liang-Ming, Yeh Chao-Bin
Department of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan.
Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan; School of Optometry, Chung Shan Medical University, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
PLoS One. 2015 Apr 10;10(4):e0122961. doi: 10.1371/journal.pone.0122961. eCollection 2015.
Fibroblast growth factor receptor 4 (FGFR4) polymorphisms are positively correlated with tumor progression in numerous malignant tumors. However, the association between FGFR4 genetic variants and the risk of hepatocellular carcinoma (HCC) has not yet been determined. In this study, we investigated the potential associations of FGFR4 single nucleotide polymorphisms (SNPs) with HCC susceptibility and its clinicopathological characteristics.
METHODOLOGY/PRINCIPAL FINDINGS: Four SNPs in FGFR4 (rs1966265, rs351855, rs2011077, and rs7708357) were analyzed among 884 participants, including 595 controls and 289 patients with HCC. The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of HCC, and the impact of these SNPs on the susceptibility and clinicopathological characteristics of HCC. After adjusting for other covariants, HCC patients who carrying at least one A genotype (GA and AA) at rs351855 were observed to have a higher risk of liver cirrhosis compared with those carrying the wild-type genotype (GG) (OR: 2.113, 95% CI: 1.188-3.831). Moreover, the patients with at least one A genotype were particularly showed a high level of alpha-fetoprotein (AFP).
Our findings suggest that genetic polymorphism in FGFR4 rs351855 may be associated with the risk of HCC coupled with liver cirrhosis and may markedly increase the AFP level in Taiwanese patients with HCC. In addition, this is the first study that evaluated the risk factors associated with FGFR4 polymorphism variants in Taiwanese patients with HCC.
成纤维细胞生长因子受体4（FGFR4）多态性与多种恶性肿瘤的肿瘤进展呈正相关。然而，FGFR4基因变异与肝细胞癌（HCC）风险之间的关联尚未确定。在本研究中，我们调查了FGFR4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。
方法/主要发现：在884名参与者中分析了FGFR4中的四个SNP（rs1966265、rs351855、rs2011077和rs7708357），其中包括595名对照者和289名HCC患者。对样本进行进一步分析，以阐明这些基因多态性与HCC风险之间的关联，以及这些SNP对HCC易感性和临床病理特征的影响。在调整其他协变量后，观察到rs351855处携带至少一个A基因型（GA和AA）的HCC患者与携带野生型基因型（GG）的患者相比，肝硬化风险更高（OR：2.113，95%CI：1.188 - 3.831）。此外，至少携带一个A基因型的患者特别显示出高水平的甲胎蛋白（AFP）。
我们的研究结果表明，FGFR4 rs351855中的基因多态性可能与HCC合并肝硬化的风险相关，并可能显著提高台湾HCC患者的AFP水平。此外，这是第一项评估台湾HCC患者中与FGFR4多态性变异相关风险因素的研究。
