Clinical validity of new genetic biomarkers of irinotecan neutropenia: An independent replication study

D. J. Crona; J. Ramirez; W. Qiao; A. J. De Graan; M. J. Ratain; R. H.N. Van Schaik; R. H.J. Mathijssen; G. L. Rosner; F. Innocenti

doi:10.1038/tpj.2015.23

Clinical validity of new genetic biomarkers of irinotecan neutropenia: An independent replication study

D. J. Crona, J. Ramirez, W. Qiao, A. J. De Graan, M. J. Ratain, R. H.N. Van Schaik, R. H.J. Mathijssen, G. L. Rosner, F. Innocenti

School of Medicine

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

The overall goal of this study was to provide evidence for the clinical validity of nine genetic variants in five genes previously associated with irinotecan neutropenia and pharmacokinetics. Variants associated with absolute neutrophil count (ANC) nadir and/or irinotecan pharmacokinetics in a discovery cohort of cancer patients were genotyped in an independent replication cohort of 108 cancer patients. Patients received single-agent irinotecan every 3 weeks. For ANC nadir, we replicated UGT1A1∗28, UGT1A1∗93 and SLCO1B1∗1b in univariate analyses. For irinotecan area under the concentration-time curve (AUC_0-24), we replicated ABCC2 -24C>T; however, ABCC2 -24C>T only predicted a small fraction of the variance. For SN-38 AUC_0-24 and the glucuronidation ratio, we replicated UGT1A1∗28 and UGT1A1∗93. In addition to UGT1A1∗28, this study independently validated UGT1A1∗93 and SLCO1B1∗1b as new predictors of irinotecan neutropenia. Further demonstration of their clinical utility will optimize irinotecan therapy in cancer patients.

Original language	English (US)
Pages (from-to)	54-59
Number of pages	6
Journal	Pharmacogenomics Journal
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/tpj.2015.23
State	Published - Feb 1 2016

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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title = "Clinical validity of new genetic biomarkers of irinotecan neutropenia: An independent replication study",

abstract = "The overall goal of this study was to provide evidence for the clinical validity of nine genetic variants in five genes previously associated with irinotecan neutropenia and pharmacokinetics. Variants associated with absolute neutrophil count (ANC) nadir and/or irinotecan pharmacokinetics in a discovery cohort of cancer patients were genotyped in an independent replication cohort of 108 cancer patients. Patients received single-agent irinotecan every 3 weeks. For ANC nadir, we replicated UGT1A1∗28, UGT1A1∗93 and SLCO1B1∗1b in univariate analyses. For irinotecan area under the concentration-time curve (AUC0-24), we replicated ABCC2 -24C>T; however, ABCC2 -24C>T only predicted a small fraction of the variance. For SN-38 AUC0-24 and the glucuronidation ratio, we replicated UGT1A1∗28 and UGT1A1∗93. In addition to UGT1A1∗28, this study independently validated UGT1A1∗93 and SLCO1B1∗1b as new predictors of irinotecan neutropenia. Further demonstration of their clinical utility will optimize irinotecan therapy in cancer patients.",

author = "Crona, {D. J.} and J. Ramirez and W. Qiao and {De Graan}, {A. J.} and Ratain, {M. J.} and {Van Schaik}, {R. H.N.} and Mathijssen, {R. H.J.} and Rosner, {G. L.} and F. Innocenti",

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AU - Ramirez, J.

AU - Qiao, W.

AU - De Graan, A. J.

AU - Ratain, M. J.

AU - Van Schaik, R. H.N.

AU - Mathijssen, R. H.J.

AU - Rosner, G. L.

AU - Innocenti, F.

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Clinical validity of new genetic biomarkers of irinotecan neutropenia: An independent replication study

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