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Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia
- Source :
- Frontiers in Pharmacology, 13, Frontiers in Pharmacology, 13. FRONTIERS MEDIA SA
- Publication Year :
- 2023
-
Abstract
- 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 p-value −5 were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in TSPAN5, RBBP4P5, AC010090.1 and RNU6-38P were suggestively associated with platinum-induced ototoxicity. The lowest p-value was found for rs7671702 in TSPAN5 (odds ratio 2.0 (95% confidence interval 1.5–2.7), p-value 5.0 × 10−7). 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.
- Subjects :
- Pharmacology
Settore BIO/14 - FARMACOLOGIA
TSPAN5
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
cisplatin
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10]
ototoxicity
All institutes and research themes of the Radboud University Medical Center
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
carboplatin
Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]
childhood cancer
GWAS
Pharmacology (medical)
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology, 13, Frontiers in Pharmacology, 13. FRONTIERS MEDIA SA
- Accession number :
- edsair.doi.dedup.....9ab554ae826822b89d939d18c4802aab