Oncotarget

Research Papers:

Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility

Chia-Hsuan Chou, Ming-Ju Hsieh, Chun-Yi Chuang, Jen-Tsun Lin, Chia-Ming Yeh, Pao-Yu Tseng, Shun-Fa Yang, Mu-Kuan Chen and Chiao-Wen Lin _

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Oncotarget. 2017; 8:96225-96238. https://doi.org/10.18632/oncotarget.21958

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Abstract

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

Correspondence to:

Chiao-Wen Lin, email: cwlin@csmu.edu.tw

Mu-Kuan Chen, email: 53780@cch.org.tw

Keywords: FGFR4; polymorphism; OSCC; metastasis; betel quid chewing

Received: August 05, 2017     Accepted: September 23, 2017     Published: October 23, 2017

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.


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