title: Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients.
abstract: VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined. We found that rs9582036 and rs9554320 showed a significant association with sunitinib PFS in the CCF cohort (HR: 0.254, 95%CI: 0.092-0.703; P=0.008 and HR: 0.430, 95%CI: 0.200-0.927; P=0.031, respectively). Patients with the variant genotype of rs9582036 and rs9554320 had a shorter median PFS. No significant association of both SNPs with sunitinib PFS or OS was detected in either the SUTOX or SOGUG cohort. After the combination of all available data into a meta-analysis, the association of both SNPs with sunitinib PFS or OS did not achieve the threshold for statistical significance. Our findings suggest that, although VEGFR1 rs9582036 and rs9554320 are involved in sunitinib therapy outcome, its clinical use as biomarkers for prediction of sunitinib outcome in mRCC patients is limited, due to inconsistent findings when analyzing all existing studies together.
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.|Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Swen
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Epie
authors.initials: E
authors.lastname: Boven
authors.affiliation: Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.|Spanish Oncology Genitourinary Group (SOGUG), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
authors.affiliation: Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.|ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Antona
authors.affiliation: Spanish Oncology Genitourinary Group (SOGUG), Madrid, Spain.|Oncology Unit, Clara Campal Comprehensive Cancer Center, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: García-Donas
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute (CCF), Cleveland, Ohio, USA.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D040281:Vascular Endothelial Growth Factor Receptor-1; D000077210:Sunitinib
keywords: VEGFR1; meta-analysis; metastatic renal cell carcinoma; sunitinib; validation study