Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma

被引：20

作者：

Diekstra, M. H. ^{[1
,2
]}

Belaustegui, A. ^{[3
]}

Swen, J. J. ^{[1
,2
]}

Boven, E. ^{[2
,4
]}

Castellano, D. ^{[5
,6
]}

Gelderblom, H. ^{[2
,7
]}

Mathijssen, R. H. ^{[2
,8
]}

Garcia-Donas, J. ^{[6
,9
]}

Rodriguez-Antona, C. ^{[10
,11
]}

Rini, B. I. ^{[12
]}

Guchelaar, H-J ^{[1
,2
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Albinusdreef 2,POB 9600,Post Zone L0-P, NL-2300 RC Leiden, Netherlands

[2] SUTOX Consortium, Dutch Working Grp Focusing Genotype Related Sunit, Leiden, Netherlands

[3] Hosp Univ Cruces, Dept Clin Pharm, Baracaldo, Bizkaia, Spain

[4] Vrije Univ Amsterdam, Dept Med Oncol, Med Ctr, Amsterdam, Netherlands

[5] Hosp Univ 12 Octubre, Dept Oncol, Madrid, Spain

[6] Spanish Oncol Genitourinary Grp, Madrid, Spain

[7] Leiden Univ, Dept Clin Oncol, Med Ctr, Leiden, Netherlands

[8] Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands

[9] Clara Campal Comprehens Canc Ctr, Oncol Unit, Madrid, Spain

[10] Spanish Natl Canc Res Ctr, Hereditary Endocrine Canc Grp, Madrid, Spain

[11] ISCIII Ctr Biomed Res Rare Dis, Madrid, Spain

[12] Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA

来源：

PHARMACOGENOMICS JOURNAL | 2017年 / 17卷 / 01期

关键词：

SINGLE NUCLEOTIDE POLYMORPHISMS; GENETIC POLYMORPHISMS; NITRIC-OXIDE; PHARMACOKINETICS; ASSOCIATION; VEGF;

D O I：

10.1038/tpj.2015.100

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The single nucleotide polymorphism (SNP) rs4646437G>A in CYP3A4 was suggested to be related to sunitinib toxicity. Our objective was to perform an in-depth investigation of the association between this SNP and sunitinib toxicity and efficacy using a large cohort of metastatic renal cell carcinoma (mRCC) patients. We collected DNA and clinical information of mRCC patients treated with sunitinib. SNP rs4646437 in CYP3A4 was tested for associations with toxicity using logistic regression. Cox regression modeling was used for association analysis of rs4646437 with progression-free survival (PFS) and overall survival (OS). In a total of 287 patients, the A-allele of CYP3A4 rs4646437 was associated with an increased risk for hypertension (odds ratio = 2.4, 95% confidence interval: 1.1-5.2, P = 0.021) and showed no significant association with PFS or OS. In conclusion, hypertension is more likely to occur in A-allele carriers of the CYP3A4 rs4646437 variant in our cohort of mRCC patients treated with sunitinib.

引用

页码：42 / 46

页数：5

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