Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.
Level 3 - non-randomized controlled study
Retrospective cohort study with cross-sectional comorbidity analysis and genome-wide association testing
PubMed 35322580 · doi:10.1002/cam4.4644
What was done
Linear and logistic regression analyses were conducted on 1,680 cisplatin-treated testicular cancer survivors without prior cranial radiotherapy to identify nongenetic risk factors for hearing loss, tinnitus, and peripheral sensory neuropathy. Genome-wide association studies (GWAS) and gene-based analyses were performed for each neurotoxicity phenotype, along with candidate replication of rs62283056 in WFS1 in an independent cohort (n = 606).
What was found
Hearing loss, tinnitus, and peripheral neuropathy were interdependent after accounting for age and cisplatin dose. Survivors with these neurotoxicities had higher rates of hypertension and poorer self-reported health. Hearing loss was positively associated with BMI and nonwork noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. Peripheral neuropathy was positively associated with persistent vertigo, tobacco use, and excess alcohol consumption. In genetic analyses, TXNRD1 reached borderline gene-based significance for hearing loss (p = 4.2 × 10⁻⁶), WFS1 rs62283056 showed marginal significance in replication (p = 0.06), and WNT8A showed a significant gene-based association with tinnitus (p = 2.5 × 10⁻⁶).
Why it matters
This study links cisplatin-induced neurotoxicities with modifiable cardiovascular and lifestyle risk factors and highlights candidate susceptibility genes (TXNRD1, WNT8A) that may guide future preventive interventions.
Limits
The cohort was restricted to male testicular cancer survivors, limiting generalizability to female and older cancer populations. Several comorbidities and exposures relied on self-report. Key genetic associations showed borderline or marginal significance and require independent functional and cohort validation.
Cited by
- supports Platinum-containing cancer chemotherapy compounds are toxic to the ear, auditory neurons, and neurons throughout the body.