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Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility.
Chou, Chia-Hsuan; Hsieh, Ming-Ju; Chuang, Chun-Yi; Lin, Jen-Tsun; Yeh, Chia-Ming; Tseng, Pao-Yu; Yang, Shun-Fa; Chen, Mu-Kuan; Lin, Chiao-Wen.
Afiliação
  • Chou CH; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • Hsieh MJ; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
  • Chuang CY; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • Lin JT; Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
  • Yeh CM; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
  • Tseng PY; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • Yang SF; Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan.
  • Chen MK; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • Lin CW; Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan.
Oncotarget ; 8(56): 96225-96238, 2017 Nov 10.
Article em En | MEDLINE | ID: mdl-29221201
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Oncotarget Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Oncotarget Ano de publicação: 2017 Tipo de documento: Article