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Hearing genes and cisplatin deafness: a pilot study
Journal article   Peer reviewed

Hearing genes and cisplatin deafness: a pilot study

Christine Knoll, Richard J H Smith, Carol Shores and Julie Blatt
The Laryngoscope, Vol.116(1), pp.72-74
01/2006
DOI: 10.1097/01.mlg.0000185596.20207.d2
PMID: 16481813

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Abstract

Cisplatin commonly is used to treat pediatric solid tumors. A major dose-limiting toxicity is sensorineural hearing loss. Which patients experience ototoxicity after treatment with cisplatin must reflect individual susceptibility, since it is not seen in all similarly treated patients. We hypothesized that mutations or polymorphisms in hearing genes are more common in patients who experience ototoxicity than in the general population. We completed retrospective mutation screening of GJB2 and SLC26A4 and screened for three mtDNA mutations in patients with a history of childhood cancer who developed severe hearing loss at cumulative cisplatin doses of less than 400 mg/M2. Patients younger than 21 years of age who experienced severe hearing loss after cisplatin were identified using the Childhood Cancer Survivor Study database. Archival DNA from buccal washes of 11 patients was used for mutation screening and detection. With the exception of one patient (9.1%) who was a carrier for the 35delG mutation, no mutant alleles were found. Given the reported prevalence of the 35delG mutation in the general population of 2.5%, this result is not significant (P = .35). It is not likely that any of the five hearing genes we examined contribute to cisplatin ototoxicity. Further study may be warranted to look at other hearing genes as possible predictors of cisplatin ototoxicity.
 Predictive Value of Tests Deafness - genetics Follow-Up Studies Humans Child, Preschool Hearing Loss, Sensorineural - epidemiology Chromatography, High Pressure Liquid Incidence Dose-Response Relationship, Drug Hearing Loss, Sensorineural - chemically induced DNA Mutational Analysis Sensitivity and Specificity Retrospective Studies Child Genetic Predisposition to Disease Risk Assessment Connexins - genetics Hearing Loss, Sensorineural - genetics Genes, Recessive Connexins - metabolism Connexin 26 Maximum Tolerated Dose Pilot Projects Cisplatin - therapeutic use Adolescent Cisplatin - adverse effects Mutation Deafness - chemically induced

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