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. García-Donas, C. Rodríguez-Antona, B. I. Rini, H. J. Guchelaar

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 - 1 Jan 2017
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors/adverse effects
  • Carcinoma, Renal Cell/drug therapy
  • Chi-Square Distribution
  • Cytochrome P-450 CYP3A/genetics
  • Disease-Free Survival
  • Europe
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Hypertension/chemically induced
  • Indoles/adverse effects
  • Kidney Neoplasms/drug therapy
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Ohio
  • Pharmacogenomic Variants
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • Protein Kinase Inhibitors/adverse effects
  • Pyrroles/adverse effects
  • Retrospective Studies
  • Risk Factors
  • Sunitinib
  • Time Factors
  • Treatment Outcome

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