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Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Hearing genes and cisplatin deafness: a pilot study
Christine Knoll1, Richard J H Smith, Carol Shores
1Division of Pediatric Hematology-Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7220, USA.
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/M2.
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.
Insights
Genetic screening did not reveal a significant link between common hearing gene mutations and cisplatin-induced ototoxicity in pediatric cancer patients. Further research into other genes is needed to predict hearing loss risk.
Area of Science:
- Pediatric Oncology
- Genetics
- Ototoxicity Research
Background:
- Cisplatin is a vital chemotherapy for pediatric solid tumors.
- Sensorineural hearing loss is a significant dose-limiting toxicity of cisplatin.
- Individual susceptibility influences cisplatin-induced ototoxicity.
Purpose of the Study:
- To investigate the hypothesis that mutations or polymorphisms in hearing genes are more prevalent in pediatric patients experiencing cisplatin ototoxicity.
- To identify potential genetic predictors of cisplatin-induced hearing loss.
Main Methods:
- Retrospective mutation screening of GJB2 and SLC26A4 genes.
- Screening for three mitochondrial DNA (mtDNA) mutations.
- Analysis of DNA from 11 pediatric patients with severe hearing loss after cisplatin treatment.
Main Results:
- Only one patient (9.1%) was a carrier for the 35delG mutation.
- This prevalence was not statistically significant compared to the general population (2.5%).
- No significant association was found between the screened genes and cisplatin ototoxicity.
Conclusions:
- The examined hearing genes (GJB2, SLC26A4, and three mtDNA mutations) are unlikely contributors to cisplatin ototoxicity.
- Further investigation into other hearing-related genes is warranted to identify predictors of cisplatin-induced hearing loss.
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