Chen Tze-Ho, Yang Shun-Fa, Liu Yu-Fan, Lin Wea-Lung, Han Chih-Ping, Wang Po-Hui
1 Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan.
2 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Reprod Sci. 2018 Jan;25(1):86-93. doi: 10.1177/1933719117702250. Epub 2017 Apr 5.
This is the first study to investigate the relationships among fibroblast growth factor receptor 4 (FGFR4) genetic polymorphisms, development of uterine cervical cancer, clinicopathological variables, and patient prognosis in Taiwanese women. Real-time polymerase chain reaction and genotyping were used to detect the genotype frequencies of 4 FGFR4 single-nucleotide polymorphisms (SNPs), rs351855 (C/T, Gly388Arg), rs2011077 (G/A), rs7708357 (G/A), and rs1966265 (Ile10Val), in 138 patients with invasive cancer, 89 with precancerous lesions of uterine cervix, and 335 normal controls. The results showed that there is no significant difference in the frequencies of FGFR4 SNPs rs351855, rs2011077, rs7708357, and 1966265 between women with cervical invasive cancer and normal controls even after controlling for age. However, significant differences existed in the distributions of the FGFR4 genetic polymorphism rs2011077, when mutant homozygotes (AA) were compared using other genotypes (GG/GA) as a reference, as well as rs1966265, when mutant homozygotes (AA) were compared using GG/GA as a reference, between women with cervical precancerous lesions and normal women even after controlling for age. In multivariate analysis, lymph node metastasis was associated with cancer recurrence, and lymph node metastasis and FGFR4 rs351855 were associated with patient survival. In conclusion, our study demonstrated that FGFR4 rs2011077 and rs1966265 are associated with the progression of cervical normal tissues to precancerous lesions in Taiwanese women. Moreover, rs351855 (Gly388Arg) is the only FGFR4 genetic polymorphism that is associated with patient survival.
这是第一项在台湾女性中探究成纤维细胞生长因子受体4(FGFR4)基因多态性、子宫颈癌发生发展、临床病理变量及患者预后之间关系的研究。采用实时聚合酶链反应和基因分型检测138例浸润性癌患者、89例子宫颈癌前病变患者及335例正常对照中4个FGFR4单核苷酸多态性(SNP),即rs351855(C/T,Gly388Arg)、rs2011077(G/A)、rs7708357(G/A)和rs1966265(Ile10Val)的基因型频率。结果显示,即使校正年龄后,子宫颈浸润癌女性与正常对照之间FGFR4的SNP rs351855、rs2011077、rs7708357和rs1966265的频率也无显著差异。然而,即使校正年龄后,子宫颈癌前病变女性与正常女性之间,当以其他基因型(GG/GA)为参照比较突变纯合子(AA)时,FGFR4基因多态性rs2011077的分布存在显著差异;当以GG/GA为参照比较突变纯合子(AA)时,rs1966265的分布也存在显著差异。多因素分析显示,淋巴结转移与癌症复发相关,淋巴结转移和FGFR4 rs351855与患者生存相关。总之,我们的研究表明,FGFR4 rs2011077和rs1966265与台湾女性子宫颈正常组织向癌前病变的进展相关。此外,rs351855(Gly388Arg)是唯一与患者生存相关的FGFR4基因多态性。