Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse

Abstract CYP2C19*2 and CYP2C19*17 might influence tamoxifen metabolism and clinical outcome. Our aim was to investigate the effect of CYP2C19 genotypes on tamoxifen concentrations and metabolic ratios (MRs) and breast cancer recurrence in a large cohort of Caucasian women. Genetic variants (CYP2D6 a...

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Autores principales:	A. B. Sanchez-Spitman, J. J. Swen, V. O. Dezentjé, D. J. A. R. Moes, H. Gelderblom, H. J. Guchelaar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/59296d30f6094050a721f97177efd78a
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spelling	oai:doaj.org-article:59296d30f6094050a721f97177efd78a2021-12-02T15:23:03ZEffect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse10.1038/s41598-020-79972-x2045-2322https://doaj.org/article/59296d30f6094050a721f97177efd78a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79972-xhttps://doaj.org/toc/2045-2322Abstract CYP2C192 and CYP2C1917 might influence tamoxifen metabolism and clinical outcome. Our aim was to investigate the effect of CYP2C19 genotypes on tamoxifen concentrations and metabolic ratios (MRs) and breast cancer recurrence in a large cohort of Caucasian women. Genetic variants (CYP2D6 and CYP2C19 genotypes), tamoxifen and metabolites concentrations, baseline characteristics, and breast cancer recurrence from the CYPTAM study (NTR1509) were used. CYP2C192 and CYP2C1917 genotypes were evaluated as alleles and as groups based on CYP2D6 genotypes (high, intermediate and low activity). Log-rank test and Kaplan–Meier analysis were used to evaluate differences in recurrence defined as relapse-free survival (RFS). Classification tree analyses (CTAs) were conducted to assess the levels of interactions per polymorphism (CYP2D6 and CYP2C19 genotypes) on endoxifen concentrations. No differences in mean concentrations and MRs were observed when comparing CYP2C19 genotypes (CYP2C191/1; CYP2C191/2; CYP2C192/2; CYP2C191/17; CYP2C1917/17; CYP2C192/17). Only significant differences (p value < 0.05) in mean concentrations and MRs were observed when comparing tamoxifen activity groups (high, intermediate and low activity). A log-rank test did not find an association across CYP2C19 genotypes (p value 0.898). CTAs showed a significant relationship between CYP2D6 and endoxifen (p value < 0.0001), but no association with CYP2C19 genotypes was found. CYP2C19 polymorphisms do not have a significant impact on tamoxifen metabolism or breast cancer relapse.A. B. Sanchez-SpitmanJ. J. SwenV. O. DezentjéD. J. A. R. MoesH. GelderblomH. J. GuchelaarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. B. Sanchez-Spitman J. J. Swen V. O. Dezentjé D. J. A. R. Moes H. Gelderblom H. J. Guchelaar Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse
description	Abstract CYP2C192 and CYP2C1917 might influence tamoxifen metabolism and clinical outcome. Our aim was to investigate the effect of CYP2C19 genotypes on tamoxifen concentrations and metabolic ratios (MRs) and breast cancer recurrence in a large cohort of Caucasian women. Genetic variants (CYP2D6 and CYP2C19 genotypes), tamoxifen and metabolites concentrations, baseline characteristics, and breast cancer recurrence from the CYPTAM study (NTR1509) were used. CYP2C192 and CYP2C1917 genotypes were evaluated as alleles and as groups based on CYP2D6 genotypes (high, intermediate and low activity). Log-rank test and Kaplan–Meier analysis were used to evaluate differences in recurrence defined as relapse-free survival (RFS). Classification tree analyses (CTAs) were conducted to assess the levels of interactions per polymorphism (CYP2D6 and CYP2C19 genotypes) on endoxifen concentrations. No differences in mean concentrations and MRs were observed when comparing CYP2C19 genotypes (CYP2C191/1; CYP2C191/2; CYP2C192/2; CYP2C191/17; CYP2C1917/17; CYP2C192/17). Only significant differences (p value < 0.05) in mean concentrations and MRs were observed when comparing tamoxifen activity groups (high, intermediate and low activity). A log-rank test did not find an association across CYP2C19 genotypes (p value 0.898). CTAs showed a significant relationship between CYP2D6 and endoxifen (p value < 0.0001), but no association with CYP2C19 genotypes was found. CYP2C19 polymorphisms do not have a significant impact on tamoxifen metabolism or breast cancer relapse.
format	article
author	A. B. Sanchez-Spitman J. J. Swen V. O. Dezentjé D. J. A. R. Moes H. Gelderblom H. J. Guchelaar
author_facet	A. B. Sanchez-Spitman J. J. Swen V. O. Dezentjé D. J. A. R. Moes H. Gelderblom H. J. Guchelaar
author_sort	A. B. Sanchez-Spitman
title	Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse
title_short	Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse
title_full	Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse
title_fullStr	Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse
title_full_unstemmed	Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse
title_sort	effect of cyp2c19 genotypes on tamoxifen metabolism and early-breast cancer relapse
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/59296d30f6094050a721f97177efd78a
work_keys_str_mv	AT absanchezspitman effectofcyp2c19genotypesontamoxifenmetabolismandearlybreastcancerrelapse AT jjswen effectofcyp2c19genotypesontamoxifenmetabolismandearlybreastcancerrelapse AT vodezentje effectofcyp2c19genotypesontamoxifenmetabolismandearlybreastcancerrelapse AT djarmoes effectofcyp2c19genotypesontamoxifenmetabolismandearlybreastcancerrelapse AT hgelderblom effectofcyp2c19genotypesontamoxifenmetabolismandearlybreastcancerrelapse AT hjguchelaar effectofcyp2c19genotypesontamoxifenmetabolismandearlybreastcancerrelapse
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Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse

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