Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients.
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.
['Liu|Xiaoyan|X|', 'Swen|Jesse J|JJ|', 'Boven|Epie|E|', 'Castellano|Daniel|D|', 'Gelderblom|Hans|H|', 'Mathijssen|Ron H J|RH|', 'Rodríguez-Antona|Cristina|C|', 'García-Donas|Jesus|J|', 'Rini|Brian I|BI|', 'Guchelaar|Henk-Jan|HJ|']
D000483:Alleles D000970:Antineoplastic Agents D002292:Carcinoma, Renal Cell D005787:Gene Frequency D014644:Genetic Variation D005838:Genotype D006801:Humans D007211:Indoles D007680:Kidney Neoplasms D009362:Neoplasm Metastasis D020641:Polymorphism, Single Nucleotide D011379:Prognosis D016016:Proportional Hazards Models D011758:Pyrroles D000077210:Sunitinib D016896:Treatment Outcome D040281:Vascular Endothelial Growth Factor Receptor-1
meta-analysis VEGFR1 sunitinib metastatic renal cell carcinoma validation study