Abstract

BackgroundFibroblast 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 FindingsFour 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).ConclusionsOur 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.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the malignant neoplasms common for causing cancer-related deaths worldwide, in Asian countries

  • Our findings suggest that genetic polymorphism in Fibroblast growth factor receptor 4 (FGFR4) rs351855 may be associated with the risk of hepatocellular carcinoma (HCC) coupled with liver cirrhosis and may markedly increase the AFP level in PLOS ONE | DOI:10.1371/journal.pone

  • This is the first study that evaluated the risk factors associated with FGFR4 polymorphism variants in Taiwanese patients with HCC

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the malignant neoplasms common for causing cancer-related deaths worldwide, in Asian countries. More than 80% of HCC cases occur in developing countries, Far East and Southeast Asia, with Taiwan having the third highest incidence rate in the world. Surgery is a critical treatment modality in the early stage of HCC. Because only 10%-20% of HCCs can be removed completely by surgery, early diagnosis and prevention can increase the survival rate if the underlying molecular mechanism is identified. The association between FGFR4 genetic variants and the risk of hepatocellular carcinoma (HCC) has not yet been determined. We investigated the potential associations of FGFR4 single nucleotide polymorphisms (SNPs) with HCC susceptibility and its clinicopathological characteristics

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