Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia
Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer T...
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Published in | Frontiers in pharmacology Vol. 13; p. 980309 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
09.01.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248). Results of both cohorts were combined in a meta-analysis. In primary analysis, patients with SIOP Boston Ototoxicity Scale grade ≥1 were considered cases, and patients with grade 0 were controls. Variants with a
-value <10
were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in
and
were suggestively associated with platinum-induced ototoxicity. The lowest
-value was found for rs7671702 in
(odds ratio 2.0 (95% confidence interval 1.5-2.7),
-value 5.0 × 10
). None of the associations were significant in the replication cohort, although the effect directions were consistent among all cohorts. Validation and functional understanding of these genetic variants could lead to more insights in the development of platinum-induced ototoxicity. |
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Bibliography: | This article was submitted to Pharmacogenetics and Pharmacogenomics, a section of the journal Frontiers in Pharmacology These authors share last authorship Reviewed by: Sofia Waissbluth, Pontificia Universidad Católica de Chile, Chile Present address: Marieke J. H. Coenen, Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, Netherlands These authors share first authorship Edited by: Robert James Hayashi, Washington University in St. Louis, United States Chih-Hao Chen, Taipei Veterans General Hospital, Taiwan |
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2022.980309 |