Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility
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Chia-Hsuan Chou1,2, Ming-Ju Hsieh1,3,4, Chun-Yi Chuang5,6, Jen-Tsun Lin5,7, Chia-Ming Yeh8, Pao-Yu Tseng8, Shun-Fa Yang1,2, Mu-Kuan Chen1,8 and Chiao-Wen Lin9,10
1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
2Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
3Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan
4Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
5School of Medicine, Chung Shan Medical University, Taichung, Taiwan
6Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan
7Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan
8Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan
9Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
10Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
Chiao-Wen Lin, email: [email protected]
Mu-Kuan Chen, email: [email protected]
Keywords: FGFR4; polymorphism; OSCC; metastasis; betel quid chewing
Received: August 05, 2017 Accepted: September 23, 2017 Published: October 23, 2017
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.
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