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Title: Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib
Authors: Beuselinck, Benoit ×
Karadimou, A
Lambrechts, D
Claes, Bram
Wolter, Pascal
Couchy, G
Berkers, Joost
Paridaens, Robert
Schöffski, Patrick
Méjean, A
Verkarre, V
Lerut, Evelyne
de la Taille, A
Tourani, J-M
Bigot, P
Linassier, C
Négrier, S
Berger, J
Patard, J-J
Zucman-Rossi, J
Oudard, S #
Issue Date: Mar-2013
Publisher: Harcourt Publishers
Series Title: British Journal of Cancer vol:108 issue:4 pages:887-900
Article number: 10.1038/bjc.2012.548
Abstract: Background:There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.Methods:We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.Results:In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).Conclusion:Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.
URI: 
ISSN: 0007-0920
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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