Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele predicts prolonged survival and platinum sensitivity in advanced ovarian cancer.
FGFR4 has been shown to play an important role in the etiology and progression of solid tumors. A single nucleotide polymorphism (SNP) within the FGFR4 gene has previously been linked to prognosis and response to chemotherapy in breast cancer and other malignancies. This study evaluates the relevance of this SNP in advanced ovarian cancer. FGFR4-genotype was analyzed in 236 patients recruited as part of the OVCAD project. Genotyping was performed on germ-line DNA using a TaqMan based genotyping assay. Results were correlated with clinicopathological variables and survival. The FGFR4 388Arg genotype was significantly associated with prolonged progression-free and overall survival (univariate: HR 0.68, p = 0.017; HR 0.49, p = 0.005; multivariate: HR 0.69, p = 0.025; HR 0.49, p = 0.006) though the positive prognostic value was restricted to patients without postoperative residual tumor. Indeed, there was a significant interaction between FGFR4 genotype and residual tumor for overall survival. Furthermore, the FGFR4 388Arg genotype significantly correlated with platinum sensitivity in the same subgroup (multivariate OR 3.81 p = 0.004). FGFR4 Arg388Gly genotype is an independent and strong context specific prognostic factor in patients with advanced ovarian cancer and could be used to predict platinum-sensitivity.
Department of Obstetrics & Gynecology, University Hospital Heidelberg, Heidelberg, Germany. frederik.marme@med.uni-heidelberg.de
Frederik
F
Marmé
Thomas
T
Hielscher
Sarah
S
Hug
Sandra
S
Bondong
Robert
R
Zeillinger
Dan Cacsire
DC
Castillo-Tong
Jalid
J
Sehouli
Ioana
I
Braicu
Ignace
I
Vergote
Cadron
C
Isabella
Sven
S
Mahner
Irmgard
I
Ferschke
Joachim
J
Rom
Christof
C
Sohn
Andreas
A
Schneeweiss
Peter
P
Altevogt
D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000737:chemistry / Q000235:genetics*; D015996:Survival Rate
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D001120:Arginine; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4