title: VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line sunitinib.
abstract: BACKGROUND
  Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients.
  
  
  METHODS
  A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS.
  
  
  CONCLUSIONS
  In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.
authors.affiliation: Department of Clinical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy. marioscartozzi@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Scartozzi
authors.forename: M
authors.initials: M
authors.lastname: Bianconi
authors.forename: L
authors.initials: L
authors.lastname: Faloppi
authors.forename: C
authors.initials: C
authors.lastname: Loretelli
authors.forename: A
authors.initials: A
authors.lastname: Bittoni
authors.forename: M
authors.initials: M
authors.lastname: Del Prete
authors.forename: R
authors.initials: R
authors.lastname: Giampieri
authors.forename: E
authors.initials: E
authors.lastname: Maccaroni
authors.forename: S
authors.initials: S
authors.lastname: Nicoletti
authors.forename: L
authors.initials: L
authors.lastname: Burattini
authors.forename: D
authors.initials: D
authors.lastname: Minardi
authors.forename: G
authors.initials: G
authors.lastname: Muzzonigro
authors.forename: R
authors.initials: R
authors.lastname: Montironi
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / 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; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics*; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib