Article

Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib

1] Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium [2] Inserm U674 Génomique fonctionnelle des tumeurs solides, Université Paris-5 René Descartes, Rue Juliette Dodu 27, 75010 Paris, France.
British Journal of Cancer (Impact Factor: 4.82). 03/2013; 108(4):887-900. DOI: 10.1038/bjc.2012.548
Source: PubMed

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.

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