Hearing genes and cisplatin deafness: A pilot study

Objective. 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. Study Design: 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/M-2. Materials and Methods: 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. Results. 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). Conclusions. 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.