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.


METHODS
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.


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.
Division of Pediatric Hematology-Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7220, USA.
Christine
C
Knoll
Richard J H
RJ
Smith
Carol
C
Shores
Julie
J
Blatt
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D003638:Deafness / Q000139:chemically induced / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D020714:Maximum Tolerated Dose; D009154:Mutation; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D002945:Cisplatin