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.
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Acknowledgements
We thank Tahar van der Straaten and Renée Baak-Pablo for their assistance with data management and genotyping. The European Union’s Seventh Framework Programme (FP7/2007–2013) supports Meta Diekstra under grant agreement no. 259939. This research is supported by Pfizer.
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Brian Rini and Garcia-Donas report consulting and research funding from Pfizer. The other authors declare no conflict of interest.
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Diekstra, M., Belaustegui, A., Swen, J. et al. Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma. Pharmacogenomics J 17, 42–46 (2017). https://doi.org/10.1038/tpj.2015.100
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DOI: https://doi.org/10.1038/tpj.2015.100
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