Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy - PubMed (original) (raw)

. 2009 Dec;41(12):1345-9.

doi: 10.1038/ng.478. Epub 2009 Nov 8.

Hagit Katzov-Eckert, Marie-Pierre Dubé, Beth Brooks, S Rod Rassekh, Amina Barhdadi, Yassamin Feroz-Zada, Henk Visscher, Andrew M K Brown, Michael J Rieder, Paul C Rogers, Michael S Phillips, Bruce C Carleton, Michael R Hayden; CPNDS Consortium

Collaborators, Affiliations

• PMID: 19898482
• DOI: 10.1038/ng.478

Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy

Colin J D Ross et al. Nat Genet. 2009 Dec.

Erratum in

• Nat Genet. 2013 May;45(5):578

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.

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Comment in

• Genetic variants associated with cisplatin-induced hearing loss.
  Pussegoda KA. Pussegoda KA. Clin Genet. 2010 Jul;78(1):33-5. doi: 10.1111/j.1399-0004.2010.01414_2.x. Clin Genet. 2010. PMID: 20597921 No abstract available.
• Challenges in interpreting the evidence for genetic predictors of ototoxicity.
  Ratain MJ, Cox NJ, Henderson TO. Ratain MJ, et al. Clin Pharmacol Ther. 2013 Dec;94(6):631-5. doi: 10.1038/clpt.2013.178. Clin Pharmacol Ther. 2013. PMID: 24241639

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