Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer

Abstract Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given...

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Autores principales:	Bo Gao, Yi Lu, Annemieke J. M. Nieuweboer, Hongmei Xu, Jonathan Beesley, Ingrid Boere, Anne-Joy M. de Graan, Peter de Bruijn, Howard Gurney, Catherine J. Kennedy, Yoke-Eng Chiew, Sharon E. Johnatty, Philip Beale, Michelle Harrison, Craig Luccarini, Don Conroy, Ron H. J. Mathijssen, Paul R. Harnett, Rosemary L. Balleine, Georgia Chenevix-Trench, Stuart Macgregor, Anna de Fazio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29e246f9ff144263bcd7bb50c52f6993
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spelling	oai:doaj.org-article:29e246f9ff144263bcd7bb50c52f69932021-12-02T15:09:11ZGenome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer10.1038/s41598-018-19590-w2045-2322https://doaj.org/article/29e246f9ff144263bcd7bb50c52f69932018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19590-whttps://doaj.org/toc/2045-2322Abstract Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given cyclically multiple blood sampling is required to adequately define drug disposition, limiting patient recruitment. We found that carboplatin and paclitaxel disposition are stable phenotypes in ovarian cancer patients and tested a genome-wide association study (GWAS) design to identify SNPs associated with chemotherapy disposition. We found highly significant SNPs in ABCC2, a known carboplatin transporter, associated with carboplatin clearance (asymptotic P = 5.2 × 106, empirical P = 1.4 × 10−5), indicating biological plausibility. We also identified novel SNPs associated with paclitaxel disposition, including rs17130142 with genome-wide significance (asymptotic P = 2.0 × 10−9, empirical P = 1.3 × 10−7). Although requiring further validation, our work demonstrated that GWAS of chemotherapeutic drug disposition can be effective, even in relatively small cohorts, and can be adopted in drug development and treatment programs.Bo GaoYi LuAnnemieke J. M. NieuweboerHongmei XuJonathan BeesleyIngrid BoereAnne-Joy M. de GraanPeter de BruijnHoward GurneyCatherine J. KennedyYoke-Eng ChiewSharon E. JohnattyPhilip BealeMichelle HarrisonCraig LuccariniDon ConroyRon H. J. MathijssenPaul R. HarnettRosemary L. BalleineGeorgia Chenevix-TrenchStuart MacgregorAnna de FazioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bo Gao Yi Lu Annemieke J. M. Nieuweboer Hongmei Xu Jonathan Beesley Ingrid Boere Anne-Joy M. de Graan Peter de Bruijn Howard Gurney Catherine J. Kennedy Yoke-Eng Chiew Sharon E. Johnatty Philip Beale Michelle Harrison Craig Luccarini Don Conroy Ron H. J. Mathijssen Paul R. Harnett Rosemary L. Balleine Georgia Chenevix-Trench Stuart Macgregor Anna de Fazio Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
description	Abstract Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given cyclically multiple blood sampling is required to adequately define drug disposition, limiting patient recruitment. We found that carboplatin and paclitaxel disposition are stable phenotypes in ovarian cancer patients and tested a genome-wide association study (GWAS) design to identify SNPs associated with chemotherapy disposition. We found highly significant SNPs in ABCC2, a known carboplatin transporter, associated with carboplatin clearance (asymptotic P = 5.2 × 106, empirical P = 1.4 × 10−5), indicating biological plausibility. We also identified novel SNPs associated with paclitaxel disposition, including rs17130142 with genome-wide significance (asymptotic P = 2.0 × 10−9, empirical P = 1.3 × 10−7). Although requiring further validation, our work demonstrated that GWAS of chemotherapeutic drug disposition can be effective, even in relatively small cohorts, and can be adopted in drug development and treatment programs.
format	article
author	Bo Gao Yi Lu Annemieke J. M. Nieuweboer Hongmei Xu Jonathan Beesley Ingrid Boere Anne-Joy M. de Graan Peter de Bruijn Howard Gurney Catherine J. Kennedy Yoke-Eng Chiew Sharon E. Johnatty Philip Beale Michelle Harrison Craig Luccarini Don Conroy Ron H. J. Mathijssen Paul R. Harnett Rosemary L. Balleine Georgia Chenevix-Trench Stuart Macgregor Anna de Fazio
author_facet	Bo Gao Yi Lu Annemieke J. M. Nieuweboer Hongmei Xu Jonathan Beesley Ingrid Boere Anne-Joy M. de Graan Peter de Bruijn Howard Gurney Catherine J. Kennedy Yoke-Eng Chiew Sharon E. Johnatty Philip Beale Michelle Harrison Craig Luccarini Don Conroy Ron H. J. Mathijssen Paul R. Harnett Rosemary L. Balleine Georgia Chenevix-Trench Stuart Macgregor Anna de Fazio
author_sort	Bo Gao
title	Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
title_short	Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
title_full	Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
title_fullStr	Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
title_full_unstemmed	Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
title_sort	genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/29e246f9ff144263bcd7bb50c52f6993
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Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer

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