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Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study
E. Clemens, L. Broer, T. Langer, AG. Uitterlinden, ACH. de Vries, M. van Grotel, SFM. Pluijm, H. Binder, J. Byrne, EVD. Broeder, M. Crocco, D. Grabow, P. Kaatsch, M. Kaiser, L. Kenborg, JF. Winther, C. Rechnitzer, H. Hasle, T. Kepak, AF. van der...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, multicentrická studie, práce podpořená grantem
NLK
ProQuest Central
od 2001-01-01 do Před 1 rokem
Open Access Digital Library
od 2001-01-01
Health & Medicine (ProQuest)
od 2001-01-01 do Před 1 rokem
- MeSH
- cisplatina škodlivé účinky MeSH
- dítě MeSH
- genetická variace genetika MeSH
- genetické asociační studie metody MeSH
- internacionalita * MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory farmakoterapie epidemiologie genetika MeSH
- nedoslýchavost chemicky indukované epidemiologie genetika MeSH
- novorozenec MeSH
- ototoxicita epidemiologie genetika MeSH
- předškolní dítě MeSH
- protinádorové látky škodlivé účinky MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8-21.5; P = 5.6 × 10-7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3-4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04-14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07-2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.
Aarhus University Hospital Department of Pediatrics Aarhus University Hospital Aarhus Denmark
Boyne Research Institute Drogheda Ireland
Danish Cancer Society Research Center Copenhagen Denmark
Department of Children Hemato Oncology Motol University Hospital Prague Prague Czech Republic
Department of Clinical Medicine Faculty of Health Aarhus University Aarhus Denmark
Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands
Department of Neurooncology Istituto Giannina Gaslini Genova Italy
Department of Pediatric Hematology and Oncology VU Medical Center Amsterdam The Netherlands
Department of Pediatric Oncology Academic Medical Center Amsterdam Amsterdam The Netherlands
Department of Pediatric Oncology Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands
Institute of Social and Preventive Medicine University of Bern Bern Switzerland
Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
Citace poskytuje Crossref.org
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