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    Nat Genet. 2009 Dec;41(12):1345-9. Epub 2009 Nov 8.

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

    Ross CJ, Katzov-Eckert H, Dubé MP, Brooks B, Rassekh SR, Barhdadi A, Feroz-Zada Y, Visscher H, Brown AM, Rieder MJ, Rogers PC, Phillips MS, Carleton BC, Hayden MR; CPNDS Consortium.

    Collaborators (61)

    Hayden M, Carleton B, Ross C, Smith A, MacLeod S, Wasserman W, Hildebrand C, Castro L, Ghannadan R, Carter C, Honeyman G, Katzov H, Rassekh R, Lau L, Lim J, Miao F, Mitton C, Ng D, Pape T, Stannard P, Visscher H, Zhang LH, Nijssen-Jordan C, Johnson D, Verbeek L, Kaczowka R, Churcher L, Grundy P, Stobart K, Wilson B, Desai S, Hall K, Chan S, Grarnham B, Staub M, Rieder M, Malkin B, Madadi P, Cranston A, Portwine C, Koren G, Ito S, Garcia F, Inoue M, Sakaguchi S, Tanaka T, Vaillancourt R, Elliott-Miller P, Mankoo H, Wong E, Wilson B, Maher M, Bussières JF, Lebel D, Barret P, Dubé MP, Phillips M, Avard D, Murray M, Boliver D, Osborne CA.

    Source

    Department of Medical Genetics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.

    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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    PMID:
    19898482
    [PubMed - indexed for MEDLINE]

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