You have accessJournal of UrologyKidney Cancer: Advanced I1 Apr 2015PD35-08 POLYMORPHISMS IN VEGFA, VEGFR1, -2 AND -3 ARE ASSOCIATED WITH RESPONSE AND OUTCOME OF SUNITINIB-TREATED METASTATIC RENAL CELL CARCINOMA PATIENTS Juana Dornbusch, Martina Walter, Andrea Gottschalk, Alice Obaje, Kerstin Junker, Carsten-Henning Ohlmann, Matthias Meinhardt, Aristeidis Zacharis, Stefan Zastrow, Marc-Oliver Grimm, Stefanie J. Klug, Susanne Fuessel, and Manfred P. Wirth Juana DornbuschJuana Dornbusch More articles by this author , Martina WalterMartina Walter More articles by this author , Andrea GottschalkAndrea Gottschalk More articles by this author , Alice ObajeAlice Obaje More articles by this author , Kerstin JunkerKerstin Junker More articles by this author , Carsten-Henning OhlmannCarsten-Henning Ohlmann More articles by this author , Matthias MeinhardtMatthias Meinhardt More articles by this author , Aristeidis ZacharisAristeidis Zacharis More articles by this author , Stefan ZastrowStefan Zastrow More articles by this author , Marc-Oliver GrimmMarc-Oliver Grimm More articles by this author , Stefanie J. KlugStefanie J. Klug More articles by this author , Susanne FuesselSusanne Fuessel More articles by this author , and Manfred P. WirthManfred P. Wirth More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2231AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Single nucleotide polymorphisms (SNPs) in angiogenesis-associated genes might play an important role in activity of the tyrosine kinase inhibitor sunitinib and could affect survival of cancer patients treated with this drug. The aim of study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, -2 and -3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC). METHODS DNA isolated from non-malignant kidney tissue specimens or lymphocytes from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan® SNP Genotyping Assays. Objective response rate was evaluated according to RECIST. Adverse effects of sunitinib treatment like hand-foot syndrome (HFS) and hypertension (HTN) were registered from medical records. RESULTS Kaplan-Meier analysis revealed a significantly reduced progression-free survival (PFS) in patients with the wild type (WT) allele of VEGFA rs699947 (p=0.017). Patients with variant alleles had a higher risk for HFS (p=0.017). Univariate analyses identified associations for the WT alleles of VEGFA rs2010963 and VEGFR3 rs307826 with poor PFS. Patients with the AA/AC-alleles of VEGFR1 rs9582036 had an improved median overall survival (OS) (42 vs 16 months, p=0.002) than those with the CC-WT allele. The CT/TT-genotypes of VEGFR2 rs2305948 were associated with shorter OS (p=0.029) and higher risk of HTN (p=0.044). Haplotype analysis displayed high linkage disequilibrium (LD) between SNPs of VEGFA, VEGFR1 and VEGFR3, respectively. Carriers of the variant alleles of the SNPs VEGFA rs20109663 (CC/CG), rs699947 (AC/CC) and rs1570360 (AA/AG) showed a significantly enhanced OS in contrast to all other allele combinations (p=0.019). CONCLUSIONS The results suggest that SNPs in genes such as VEGFA, VEGFR1, -2 and -3 are associated with survival after sunitinib therapy or adverse effects and might be predictive markers in mRCC therapy. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e762 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juana Dornbusch More articles by this author Martina Walter More articles by this author Andrea Gottschalk More articles by this author Alice Obaje More articles by this author Kerstin Junker More articles by this author Carsten-Henning Ohlmann More articles by this author Matthias Meinhardt More articles by this author Aristeidis Zacharis More articles by this author Stefan Zastrow More articles by this author Marc-Oliver Grimm More articles by this author Stefanie J. Klug More articles by this author Susanne Fuessel More articles by this author Manfred P. Wirth More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...