title: FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung.
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.
authors.affiliation: Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Felicia S
authors.initials: FS
authors.lastname: Falvella
authors.forename: Elisa
authors.initials: E
authors.lastname: Frullanti
authors.forename: Antonella
authors.initials: A
authors.lastname: Galvan
authors.forename: Monica
authors.initials: M
authors.lastname: Spinola
authors.forename: Sara
authors.initials: S
authors.lastname: Noci
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.forename: Mario
authors.initials: M
authors.lastname: Nosotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Santambrogio
authors.forename: Matteo
authors.initials: M
authors.lastname: Incarbone
authors.forename: Marco
authors.initials: M
authors.lastname: Alloisio
authors.forename: Elisa
authors.initials: E
authors.lastname: Calabrò
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Vidar
authors.initials: V
authors.lastname: Skaug
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; C117476:FGF19 protein, human; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D012333:RNA, Messenger; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4