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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pussegoda, K. Ross, C. J. Visscher, H. Yazdanpanah, M. Brooks, B. Rassekh, S. R. Zada, Y. F. Dubé, M-P Carleton, B. C. Hayden, M. R. |
| Organization | CPNDS Consortium |
| Description | Country affiliation: Canada Author Affiliation: Pussegoda K ( Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.) |
| Abstract | Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. A serious complication of cisplatin treatment is permanent hearing loss. The aim of this study was to replicate previous genetic findings in an independent cohort of 155 pediatric patients. Associations were replicated for genetic variants in TPMT (rs12201199, P = 0.0013, odds ratio (OR) 6.1) and ABCC3 (rs1051640, P = 0.036, OR 1.8). A predictive model combining variants in TPMT, ABCC3, and COMT with clinical variables (patient age, vincristine treatment, germ-cell tumor, and cranial irradiation) significantly improved the prediction of hearing-loss development as compared with using clinical risk factors alone (area under the curve (AUC) 0.786 vs. 0.708, P = 0.00048). The novel combination of genetic and clinical factors predicted the risk of hearing loss with a sensitivity of 50.3% and a specificity of 92.7%. These findings provide evidence to support the importance of TPMT, COMT, and ABCC3 in the prediction of cisplatin-induced hearing loss in children. |
| File Format | HTM / HTML |
| ISSN | 00099236 |
| e-ISSN | 15326535 |
| DOI | 10.1038/clpt.2013.80 |
| Journal | Clinical Pharmacology & Therapeutics |
| Issue Number | 2 |
| Volume Number | 94 |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2013-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Pharmacology Antineoplastic Agents Toxicity Cisplatin Hearing Loss Chemically Induced Methyltransferases Genetics Multidrug Resistance-associated Proteins Adolescent Catechol O-methyltransferase Child, Preschool Craniospinal Irradiation Dose-response Relationship, Drug Genetic Variation Genotype Infant Infant, Newborn Risk Factors Sensitivity And Specificity Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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