Fibroblast growth factor receptor 4 polymorphism is associated with liver cirrhosis in hepatocarcinoma

PLoS One. 2015 Apr 10;10(4):e0122961. doi: 10.1371/journal.pone.0122961. eCollection 2015.

Abstract

Background: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Asian People / genetics
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Case-Control Studies
  • DNA / analysis
  • DNA / isolation & purification
  • Female
  • Genotype
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology*
  • Liver Neoplasms / complications
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Real-Time Polymerase Chain Reaction
  • Receptor, Fibroblast Growth Factor, Type 4 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 4 / metabolism
  • Risk Factors
  • Taiwan
  • alpha-Fetoproteins / analysis

Substances

  • alpha-Fetoproteins
  • DNA
  • Receptor, Fibroblast Growth Factor, Type 4

Grants and funding

This study was supported by research grants from Chung Shan Medical University Hospital, (CSH-2014-C-019) and Chung Shan Medical University Hospital and Chi-Mei Foundation Medical Center (CSMU-CMMC-103-06). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.