BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1577072
Comparison of associations suggests mainly distinct pools of genetic risk factors contribute to cisplatin-induced hearing loss and hearing difficulty in the general population
Provisionally accepted
- 1Department of Medicine, University of Chicago, Chicago, Illinois, United States
- 2Department of Biology, Loyola University Chicago, Chicago, Illinois, United States
- 3Departments of Medical Engineering and Communication Sciences and Disorders, Global Center for Hearing and Speech Research, University of South Florida, Tampa, United States
- 4Department of Medical Oncology, Indiana University, Indianapolis, United States
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Cisplatin is an effective chemotherapeutic agent for treating many cancers. However, a major complication associated with cisplatin treatment is ototoxicity. Since the early 2000s, several genetic risk factors linked to cisplatin ototoxicity have been reported. However, the extent to which these genetic risk factors might be shared with those contributing to hearing difficulty in the general population remains unknown. In this study, we investigate if variants with reported links to increased risk of ototoxicity in cisplatin-treated cancer cohorts were also associated with hearing impairment in the general population in the results from a recent meta-analysis (Meta-study; 501,825 participants). Importantly, no significant associations were identified. We also compared association results from our recent genome-wide association study (GWAS) for hearing loss in male testicular cancer survivors (Pt-study; 1071 participants) with those from both Meta-study and a meta-analysis of the male subset (Male-study; 223,081 participants). We observed evidence for colocalization at the rs7952909 locus across the Male-study and Pt-study results, however with opposite direction of effect. Across pairwise comparisons, only two variants with matching directions of effect reached significance when relaxed selection thresholds (10 -3 or 10 -4 ) were used. Collectively, our results suggest that genetic risk factors for cisplatin-induced ototoxicity and those for hearing difficulty in the general population are largely distinct.
Keywords: Cisplatin, Cancer, Hearing Loss, ototoxicity, genetic risk
Received: 14 Feb 2025; Accepted: 27 Jun 2025.
Copyright: © 2025 Shahbazi, Wheeler, Zhang, Frisina, Travis and Dolan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: M. Eileen Dolan, Department of Medicine, University of Chicago, Chicago, Illinois, United States
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