Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.
Abstract | PURPOSE: METHODS: RESULTS:
Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self-reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork-related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10-6 ) in gene-based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort (p = 0.06; n = 606). Gene-based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10-6 ), encoding a signaling protein important in germ cell tumors. CONCLUSIONS: Genetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.
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Authors | Xindi Zhang, Matthew R Trendowski, Emma Wilkinson, Mohammad Shahbazi, Paul C Dinh, Megan M Shuey, Regeneron Genetics Center, Darren R Feldman, Robert J Hamilton, David J Vaughn, Chunkit Fung, Christian Kollmannsberger, Robert Huddart, Neil E Martin, Victoria A Sanchez, Robert D Frisina, Lawrence H Einhorn, Nancy J Cox, Lois B Travis, M Eileen Dolan |
Journal | Cancer medicine
(Cancer Med)
Vol. 11
Issue 14
Pg. 2801-2816
(07 2022)
ISSN: 2045-7634 [Electronic] United States |
PMID | 35322580
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Copyright | © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. |
Chemical References |
- Antineoplastic Agents
- Cisplatin
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Topics |
- Antineoplastic Agents
(adverse effects)
- Cisplatin
(therapeutic use)
- Genome-Wide Association Study
- Hearing Loss
(chemically induced, genetics)
- Humans
- Male
- Neurotoxicity Syndromes
- Peripheral Nervous System Diseases
(chemically induced, genetics)
- Pharmacogenetics
- Sensation Disorders
- Testicular Neoplasms
(genetics)
- Tinnitus
(chemically induced, genetics)
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