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

doi:10.1038/tpj.2015.100

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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

20 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	42-46
Aantal pagina's	5
Tijdschrift	Pharmacogenomics Journal
Volume	17
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/tpj.2015.100
Status	Gepubliceerd - 1 jan. 2017
Extern gepubliceerd	Ja

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10.1038/tpj.2015.100

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Diekstra, M. H., Belaustegui, A., Swen, J. J., Boven, E., Castellano, D., Gelderblom, H., Mathijssen, R. H., García-Donas, J., Rodríguez-Antona, C., Rini, B. I., & Guchelaar, H. J. (2017). Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma. Pharmacogenomics Journal, 17(1), 42-46. https://doi.org/10.1038/tpj.2015.100

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title = "Sunitinib-induced hypertension in CYP3A4 rs4646437 A-allele carriers with metastatic renal cell carcinoma",

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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author = "Diekstra, {M. H.} and A. Belaustegui and Swen, {J. J.} and E. Boven and D. Castellano and H. Gelderblom and Mathijssen, {R. H.} and J. Garc{\'i}a-Donas and C. Rodr{\'i}guez-Antona and Rini, {B. I.} and Guchelaar, {H. J.}",

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doi = "10.1038/tpj.2015.100",

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AU - Belaustegui, A.

AU - Swen, J. J.

AU - Boven, E.

AU - Castellano, D.

AU - Gelderblom, H.

AU - Mathijssen, R. H.

AU - García-Donas, J.

AU - Rodríguez-Antona, C.

AU - Rini, B. I.

AU - Guchelaar, H. J.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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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KW - Disease-Free Survival

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KW - Female

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DO - 10.1038/tpj.2015.100

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

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