Abstract
Aberrations of the fibroblast growth factor receptor 4 (FGFR4) genomic region include amplification of FGFR4, activation of FGFR4 kinase domain mutations, and overexpression of FGFR4, which lead to sustained cell proliferation and contribute to tumor development. However, the association between FGFR4 single-nucleotide polymorphisms (SNPs) and risk of oral squamous cell carcinoma (OSCC) remains to be determined. We investigated the relationships between FGFR4 genetic polymorphisms, OSCC development and clinicopathological variables. We recruited a total of 955 patients with OSCC and 1191 controls. Four SNPs of FGFR4 (rs2011077, rs351855, rs7708357, and rs1966265) were examined using real-time polymerase chain reaction. We found that with the rs351855 GA genotype and a combination of the GA and AA genotypes exhibited a 1.431-fold (95% CI: 1.092-1.876) and 1.335-fold (95% CI: 1.033-1.725) higher risk of OSCC. However, patients with OSCC with a homozygous A/A genotype of FGFR4 rs351855 polymorphism had a lower risk of advanced stage OSCC (P = 0.0252). Furthermore, the patients with the FGFR4 rs351855/rs1966265 A-A haplotype had a 2.890-fold (95% confidence interval [CI]: 2.257–3.700) higher risk of OSCC than the controls. Betel quid chewers with the A-A haplotype had a considerably higher risk (95% CI: 16.159–26.937) of OSCC than did betel quid nonchewers with other haplotypes. Moreover, an additional integrated in silico analysis proposed that rs351855 G allele variant to the A allele exhibited a relatively low energy of the transmembrane region. In conclusion, our results suggest that the FGFR4 rs351855 may play a role in susceptibility for OSCC development.
Highlights
Fibroblast growth factor receptors (FGFRs) modulate some crucial biological processes, such as cell proliferation, cell differentiation and tissue repair [1,2,3]
Another of our previous studies revealed that fibroblast growth factor receptor 4 (FGFR4) rs2011077 and rs1966265 were associated with the progression of normal cervical tissues to precancerous lesions in Taiwanese women, and FGFR4 rs351855 was associated with poor patient survival [10]
After adjustment for several variables, the data shown that participants with the rs351855 GA genotype and a combination of the GA and AA genotypes exhibited a 1.431-fold and 1.335-fold higher risk of oral squamous cell carcinoma (OSCC), respectively, than wild-type homozygous participants
Summary
Fibroblast growth factor receptors (FGFRs) modulate some crucial biological processes, such as cell proliferation, cell differentiation and tissue repair [1,2,3]. Our previous study revealed that FGFR4 rs351855 might be related with the risk of hepatocellular carcinoma (HCC) associated with liver cirrhosis and might increase the alpha-fetoprotein level in Taiwanese patients with HCC [9]. Another of our previous studies revealed that FGFR4 rs2011077 and rs1966265 were associated with the progression of normal cervical tissues to precancerous lesions in Taiwanese women, and FGFR4 rs351855 was associated with poor patient survival [10]
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