Beth Brooks

Publications (3)77.11 Total impact

• Article: Replication of TPMT and ABCC3 genetic variants highly associated with cisplatin-induced hearing loss in children.

  Kusala Pussegoda, Colin J Ross, Henk Visscher, Mojgan Yazdanpanah, Beth Brooks, S Rod Rassekh, Yassamin Feroz Zada, Marie-Pierre Dubé, Bruce C Carleton, Michael R Hayden
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  ABSTRACT: Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumours. 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, 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 tumour and cranial irradiation) significantly improved the prediction of developing hearing loss compared to clinical risk factors alone (AUC 0.786 vs. 0.708, P=0.00048). A novel combination of the genetic and clinical factors predicted patients at high risk of hearing loss with a sensitivity of 50.3% and a specificity of 92.7%. These findings provide evidence for the importance of TPMT, COMT and ABCC3 in the prediction of cisplatin-induced hearing loss in children.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 10 April 2013 doi:10.1038/clpt.2013.80.
  Clinical Pharmacology &#38 Therapeutics 04/2013; · 6.04 Impact Factor
• Article: Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy

  Colin J D Ross, Hagit Katzov-Eckert, Marie-Pierre Dub|[eacute, 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
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  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
  Nature Genetics 11/2009; 41(12):1345-1349. · 35.53 Impact Factor
• Source

  Available from: Michael J Rieder

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

  Colin J D Ross, 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
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  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.
  Nature Genetics 11/2009; 41(12):1345-9. · 35.53 Impact Factor