Spinola Monica, Leoni Vera, Pignatiello Carmen, Conti Barbara, Ravagnani Fernando, Pastorino Ugo, Dragani Tommaso A
Department of Experimental Oncology, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy.
J Clin Oncol. 2005 Oct 10;23(29):7307-11. doi: 10.1200/JCO.2005.17.350. Epub 2005 Aug 1.
Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand-induced tyrosine kinase activity. The Gly388Arg polymorphism in the FGFR4 gene was reported to modulate cancer cell migration in vitro and to be associated with breast, colon, and prostate cancer prognostic parameters. The purpose of this study was to investigate the involvement of the FGFR4 polymorphism in lung tumorigenesis.
A case-control study was performed including 274 patients with histologically confirmed lung adenocarcinoma and 401 healthy control subjects from general population. mRNA expression analysis was carried out in healthy lung of cancer patients.
Patients with the Arg/Arg or Gly/Arg genotype compared to those with a Gly/Gly genotype had an earlier age at cancer onset (median age, 60.2 v 63.4 years), higher proportion of poor clinical stage disease (hazard ratio [HR], 2.3; 95% CI, 1.4 to 3.9; P = .002), of nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.2; P = .027), or of short-term survivors (HR, 1.6; 95% CI, 1.1 to 2.3; P = .008). In healthy lungs, FGFR4 did not show allele-specific expression and mRNA levels were not associated with genotype.
This study suggests that FGFR4 Gly388Arg polymorphism may predict prognosis in lung adenocarcinoma.
成纤维细胞生长因子受体4（FGFR4）是具有配体诱导酪氨酸激酶活性的跨膜受体家族成员。据报道，FGFR4基因中的Gly388Arg多态性可在体外调节癌细胞迁移，并与乳腺癌、结肠癌和前列腺癌的预后参数相关。本研究的目的是调查FGFR4多态性在肺肿瘤发生中的作用。
进行了一项病例对照研究，纳入274例经组织学确诊的肺腺癌患者和401名来自普通人群的健康对照者。对癌症患者的健康肺组织进行mRNA表达分析。
与Gly/Gly基因型患者相比，Arg/Arg或Gly/Arg基因型患者的癌症发病年龄更早（中位年龄，60.2岁对63.4岁），临床分期差的疾病比例更高（风险比[HR]，2.3；95%置信区间，1.4至3.9；P = 0.002），淋巴结受累比例更高（HR，1.9；95%置信区间，1.1至3.2；P = 0.027），或短期存活者比例更高（HR，1.6；95%置信区间，1.1至2.3；P = 0.008）。在健康肺组织中，FGFR4未显示等位基因特异性表达，mRNA水平与基因型无关。
本研究表明，FGFR4 Gly388Arg多态性可能预测肺腺癌的预后。
