Genetic polymorphisms in ABCG2 and CYP1A2 are associated with imatinib dose reduction in patients treated for gastrointestinal stromal tumors

Michiel C. Verboom*, Jacqueline S.L. Kloth, Jesse J. Swen, Stefan Sleijfer, Anna K.L. Reyners, Neeltje Steeghs, Ron H.J. Mathijssen, Hans Gelderblom, Henk Jan Guchelaar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Imatinib has a mild toxicity profile, although severe adverse events may develop. In this pharmacogenetic pathway analysis the need for dose reduction and cessation of therapy was tested for an association with single nucleotide polymorphisms (SNPs) in genes related to imatinib pharmacology. Retrospective data from 315 patients with a gastrointestinal stromal tumor who received imatinib 400 mg o.d. was associated with 36 SNPs. SNPs that showed a trend in univariate testing were tested in a multivariate model with clinical factors and correction for multiple testing was performed. Dose reduction was associated with carriership of the A-allele in rs2231137 in ABCG2 (OR 7.35, p = 0.0002) and two C-alleles in rs762551 in CYP1A2 (OR 7.12, p = 0.001). Results remained significant after correction for multiple testing. Therapy cessation did not show an association with any of the tested SNPs. These results may help identifying patients at increased risk for toxicity who could benefit from intensified follow-up.

Original languageEnglish
Pages (from-to)473-479
Number of pages7
JournalPharmacogenomics Journal
Volume19
Issue number5
DOIs
Publication statusPublished - Oct 2019

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© 2019, Springer Nature Limited.

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  • EMC MM-03-86-08

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