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

Autor: Hans Gelderblom, Henk-Jan Guchelaar, Jacqueline S. L. Kloth, Neeltje Steeghs, Stefan Sleijfer, Michiel C. Verboom, Ron H.J. Mathijssen, Anna K.L. Reyners, Jesse J. Swen
Přispěvatelé: Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), Medical Oncology
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncology
030226 pharmacology & pharmacy
0302 clinical medicine
ATP Binding Cassette Transporter
Subfamily G
Member 2
Medicine
Stromal tumor
Gastrointestinal Neoplasms
Aged
80 and over
Sunitinib
ABCB1
Middle Aged
CANCER
Neoplasm Proteins
Imatinib Mesylate
Molecular Medicine
Female
medicine.drug
PROGRESSION-FREE SURVIVAL
Adult
medicine.medical_specialty
CLINICAL-RELEVANCE
Adolescent
Gastrointestinal Stromal Tumors
ANGIOGENESIS-RELATED GENES
MESYLATE
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
SUNITINIB
Young Adult
03 medical and health sciences
Cytochrome P-450 CYP1A2
Internal medicine
Genetics
Humans
Clinical significance
Progression-free survival
Adverse effect
CHRONIC MYELOID-LEUKEMIA
Aged
Retrospective Studies
Pharmacology
business.industry
Imatinib
EFFICACY
030104 developmental biology
business
Pharmacogenetics
RESISTANCE
Zdroj: Pharmacogenomics Journal
Pharmacogenomics Journal, 19(5), 473-479. NATURE PUBLISHING GROUP
Pharmacogenomics journal, 19(5), 473-479. Nature Publishing Group
Pharmacogenomics Journal, 19(5), 473-479. Nature Publishing Group
ISSN: 1470-269X
Popis: 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.
Databáze: OpenAIRE
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