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

M. H. Diekstra, A. Belaustegui, J. J. Swen, E. Boven, D. Castellano, H. Gelderblom, R. H. Mathijssen, J. Garcia-Donas, C. Rodriguez-Antona, B. I. Rini, H-J Guchelaar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)

Abstract

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.

Original languageEnglish
Pages (from-to)42-46
Number of pages5
JournalPharmacogenomics Journal
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 2017

Keywords

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

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