title: Polymorphisms in endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) predict sunitinib-induced hypertension.
abstract: Hypertension is an important side effect of sunitinib treatment. In a retrospective study in 255 patients, single-nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor (VEGFR)-2, endothelin-1 (ET-1), and endothelium-derived nitric oxide synthase (eNOS) were multivariately tested against hypertension grades and changes in systolic blood pressure (SBP), diastolic BP (DBP), and mean arterial BP (MAP). Next, the association between hypertension and survival in patients with metastatic renal cell cancer (mRCC) was studied. Greater elevations in SBP and MAP were associated with the presence of a haplotype in VEGFA (P = 0.014 and P = 0.036, respectively). The tendency to develop grade 3 hypertension was associated with this haplotype and also with a SNP in eNOS (P = 0.031 and P = 0.045, respectively). In mRCC patients, sunitinib-induced hypertension was found to confer a survival benefit, with the mean overall survival being prolonged by 7.2 months (P = 0.035 and P = 0.026 for SBP and DBP elevations, respectively). Genetic polymorphisms in VEGFA and eNOS independently predict rise in BP and/or development of severe hypertension in sunitinib-treated patients. Grade 3 hypertension was found to be an independent factor for overall survival in patients with mRCC.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. k.eechoute@erasmusmc.nl
authors.forename: K
authors.initials: K
authors.lastname: Eechoute
authors.forename: A A M
authors.initials: AA
authors.lastname: van der Veldt
authors.forename: S
authors.initials: S
authors.lastname: Oosting
authors.forename: M H W
authors.initials: MH
authors.lastname: Kappers
authors.forename: J A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.forename: H-J
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: A K L
authors.initials: AK
authors.lastname: Reyners
authors.forename: C M L
authors.initials: CM
authors.lastname: van Herpen
authors.forename: J B
authors.initials: JB
authors.lastname: Haanen
authors.forename: R H J
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: E
authors.initials: E
authors.lastname: Boven
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics* / Q000401:mortality; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D000077210:Sunitinib; D015996:Survival Rate / Q000639:trends; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib