FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung

Felicia S. Falvella, Elisa Frullanti, Antonella Galvan, Monica Spinola, Sara Noci, Loris De Cecco, Mario Nosotti, Luigi Santambrogio, Matteo Incarbone, Marco Alloisio, Elisa Calabrò, Ugo Pastorino, Vidar Skaug, Aage Haugen, Emanuela Taioli, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

Original languageEnglish
Pages (from-to)2880-2885
Number of pages6
JournalInternational Journal of Cancer
Volume124
Issue number12
DOIs
Publication statusPublished - Jun 15 2009

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Keywords

  • Genetic susceptibility
  • Lung adenocarcinoma
  • Single nucleotide polymorphisms
  • Tumor progression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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