title: Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib.
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).
  
  
  CONCLUSIONS
  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.
authors: Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. benoit.beuselinck@uzleuven.be
authors: B
authors: B
authors: Beuselinck
authors: A
authors: A
authors: Karadimou
authors: D
authors: D
authors: Lambrechts
authors: B
authors: B
authors: Claes
authors: P
authors: P
authors: Wolter
authors: G
authors: G
authors: Couchy
authors: J
authors: J
authors: Berkers
authors: R
authors: R
authors: Paridaens
authors: P
authors: P
authors: Schöffski
authors: A
authors: A
authors: Méjean
authors: V
authors: V
authors: Verkarre
authors: E
authors: E
authors: Lerut
authors: A
authors: A
authors: de la Taille
authors: J-M
authors: JM
authors: Tourani
authors: P
authors: P
authors: Bigot
authors: C
authors: C
authors: Linassier
authors: S
authors: S
authors: Négrier
authors: J
authors: J
authors: Berger
authors: J-J
authors: JJ
authors: Patard
authors: J
authors: J
authors: Zucman-Rossi
authors: S
authors: S
authors: Oudard
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib