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- Title
Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy.
- Authors
Ross, Colin J. D.; Katzov-Eckert, Hagit; Dubé, Marie-Pierre; Brooks, Beth; Rassekh, S. Rod; Barhdadi, Amina; Feroz-Zada, Yassamin; Visscher, Henk; Brown, Andrew M. K.; Rieder, Michael J.; Rogers, Paul C.; Phillips, Michael S.; Carleton, Bruce C.; Hayden, Michael R.
- Abstract
Cisplatin is a widely used and effective chemotherapeutic agent, although its use is restricted by the high incidence of irreversible ototoxicity associated with it. In children, cisplatin ototoxicity is a serious and pervasive problem, affecting more than 60% of those receiving cisplatin and compromising language and cognitive development. Candidate gene studies have previously reported associations of cisplatin ototoxicity with genetic variants in the genes encoding glutathione S-transferases and megalin. We report association analyses for 220 drug-metabolism genes in genetic susceptibility to cisplatin-induced hearing loss in children. We genotyped 1,949 SNPs in these candidate genes in an initial cohort of 54 children treated in pediatric oncology units, with replication in a second cohort of 112 children recruited through a national surveillance network for adverse drug reactions in Canada. We identified genetic variants in TPMT (rs12201199, P value = 0.00022, OR = 17.0, 95% CI 2.3–125.9) and COMT (rs9332377, P value = 0.00018, OR = 5.5, 95% CI 1.9–15.9) associated with cisplatin-induced hearing loss in children.
- Subjects
HUMAN genetic variation; CISPLATIN; DRUG therapy; DEAFNESS in children; EAR infections; OTOTOXICITY
- Publication
Nature Genetics, 2009, Vol 41, Issue 12, p1345
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.478