Evaluation of polymorphisms in angiogenesis-related genes as predictive and prognostic markers for sunitinib-treated metastatic renal cell carcinoma patients

• Published in: Journal of cancer research and clinical oncology 2016-06, Vol.142 (6), p.1171-1182
• Main Authors: Dornbusch, Juana, Walter, Martina, Gottschalk, Andrea, Obaje, Alice, Junker, Kerstin, Ohlmann, Carsten-Henning, Meinhardt, Matthias, Zacharis, Aristeidis, Zastrow, Stefan, Schoffer, Olaf, Grimm, Marc-Oliver, Klug, Stefanie J., Wirth, Manfred P., Fuessel, Susanne
• Format: Article
• Language: English
• Subjects: Aged; Angiogenesis; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - therapeutic use; Biomarkers; Biomarkers, Tumor - genetics; Cancer Research; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Female; Genes; Hematology; Humans; Indoles - therapeutic use; Internal Medicine; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Neovascularization, Pathologic - genetics; Oncology; Original Article – Cancer Research; Polymorphism; Polymorphism, Single Nucleotide; Prognosis; Pyrroles - therapeutic use; Receptors, Vascular Endothelial Growth Factor - genetics; Vascular Endothelial Growth Factor A - genetics
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-016-2137-0

Purpose 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 this retrospective study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, VEGFR2 and VEGFR3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC). Methods DNA from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan genotyping assays. Disease control rate was evaluated according to RECIST. Adverse effects of sunitinib were registered from medical records. The results of Cox and logistic regression were verified by correction for multiple testing. Results Kaplan–Meier analysis revealed a reduced progression-free survival in patients with the wild-type (WT) allele of the VEGFA SNP rs699947 compared to variant alleles. Patients with the AA/AC-alleles of the VEGFR1 SNP rs9582036 had an improved median overall survival compared to those with the CC–WT allele what could be confirmed by multivariable Cox proportional hazard regression analyses. No statistically significant associations between the analyzed SNPs and higher risk for adverse effects were observed. Conclusions The results of this study suggest that most of the selected SNPs in angiogenesis-related genes are not associated with survival of mRCC patients after sunitinib therapy or with adverse effects. Only the VEGFR1 SNP rs9582036 showed a statistically significant association with overall survival. The potential of SNPs as prognostic and predictive markers for sunitinib-treated mRCC patients should be finally assessed by prospective studies.