Document Detail


Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib.
MedLine Citation:
PMID:  21882181     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Biomarkers that predict response or toxicity to antiangiogenic therapy are sought to favorably inform the risk/benefit ratio. This study evaluated the association of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) genetic polymorphisms with the development of hypertension (HTN) and clinical outcome in metastatic clear cell renal cell carcinoma (MCCRCC) patients treated with sunitinib.
PATIENT AND METHODS: Sixty-three MCCRCC patients receiving sunitinib (50 mg 4/2) with available blood pressure (BP) data and germline DNA were retrospectively identified. A panel of candidate VEGF and VEGFR2 single nucleotide polymorphisms (SNPs) were evaluated for associations with the development of hypertension and clinical outcome.
RESULTS: VEGF SNP -634 genotype was associated with the prevalence and duration of sunitinib-induced hypertension (as defined by systolic pressure ≥150 mmHg and/or diastolic pressure ≥90 mmHg) in both univariable analysis (P = .03 and .01, respectively) and multivariable analysis, which adjusted for baseline BP and use of antihypertension medication (P = .05 and .02, respectively). Patients with the GG genotype were estimated to have a greater likelihood of being hypertensive during treatment compared with patients with the CC genotype (odds ratio of 13.62, 95% confidence interval [CI] 3.71-50.04). No single VEGF or VEGFR SNPs were found to correlate with clinical outcome. However, the combination of VEGF SNP 936 and VEGFR2 SNP 889 were associated with overall survival after adjustment for prognostic risk group (P = .03).
CONCLUSIONS: In MCCRCC patients treated with sunitinib, VEGF SNP -634 is associated with hypertension and a combination of VEGF SNP 936 and VEGFR2 SNP 889 genotypes is associated with overall survival.
Authors:
Jenny J Kim; Susan A J Vaziri; Brian I Rini; Paul Elson; Jorge A Garcia; Robert Wirka; Robert Dreicer; Mahrukh K Ganapathi; Ram Ganapathi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-31
Journal Detail:
Title:  Cancer     Volume:  118     ISSN:  1097-0142     ISO Abbreviation:  Cancer     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-20     Completed Date:  2012-05-07     Revised Date:  2014-08-19    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1946-54     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American Cancer Society.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Carcinoma, Renal Cell / complications,  drug therapy*,  genetics,  secondary
Female
Humans
Hypertension / chemically induced*,  genetics*
Indoles / adverse effects*
Kidney Neoplasms / drug therapy*,  genetics,  pathology
Male
Middle Aged
Pyrroles / adverse effects*
Treatment Outcome
Vascular Endothelial Growth Factor A / genetics*
Vascular Endothelial Growth Factor Receptor-2 / genetics*
Grant Support
ID/Acronym/Agency:
5P30CA043703/CA/NCI NIH HHS; P30 CA006973/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Indoles; 0/Pyrroles; 0/Vascular Endothelial Growth Factor A; 0/sunitinib; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2
Comments/Corrections

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