Originally published as JCO Early Release 10.1200/JCO.2005.17.350 on August 1 2005

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Functional FGFR4 Gly388Arg Polymorphism Predicts Prognosis in Lung Adenocarcinoma Patients

Monica Spinola, Vera Leoni, Carmen Pignatiello, Barbara Conti, Fernando Ravagnani, Ugo Pastorino, Tommaso A. Dragani

From the Department of Experimental Oncology and Laboratories, Thoracic Surgery, Istituto Nazionale Tumori, Milan, Italy

Address reprint requests to Tommaso A. Dragani, Department of Experimental Oncology, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy; e-mail: dragani{at}istitutotumori.mi.it.

PURPOSE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: This study suggests that FGFR4 Gly388Arg polymorphism may predict prognosis in lung adenocarcinoma.

Supported in part by grants from Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) and Fondo Investimenti Ricerca de Base (FIRB).

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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