ArticleInternational journal of clinical pharmacy2026
Inherited immune traits and cisplatin-induced ototoxicity in cancer patients: a Mendelian randomization study.
Article in International journal of clinical pharmacy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionCisplatin is a cornerstone chemotherapeutic agent frequently associated with dose-limiting ototoxicity. Increasing evidence suggests that immune-mediated mechanisms may influence interindividual susceptibility to this adverse effect; however, the role of inherited immune traits remains poorly understood.
aimThis study aimed to evaluate the causal relationship between 33 inherited immune traits and cisplatin-induced ototoxicity using Mendelian randomization (MR), and to identify age-stratified susceptibility markers in pediatric and adult cancer survivors.
methodMR was used to assess the causal effects of genetically predicted immune traits on cisplatin-induced ototoxicity. Single-nucleotide polymorphisms associated with immune traits were selected from large-scale genome-wide association study datasets. The primary analysis used the inverse variance weighted method with MR-Egger, weighted median, weighted mode, and MR-PRESSO as the sensitivity approaches. Bidirectional MR and sensitivity analyses were conducted to assess robustness and rule out reverse causation. Bonferroni correction was employed to minimize potential false-positive findings (P < 0.05/165 ≈ 0.0003).
resultsTransforming Growth Factor-beta principal component analysis (TGF-β PCA) showed an age-stratified effect: it was associated with increased risk of hearing loss in pediatric patients (OR (95% CI): 1.0 × 10
conclusionInherited immune traits, particularly TGF-β PCA, PD-1, and TCM cells, exhibit age-stratified causal effects on cisplatin-induced ototoxicity. These findings suggest the use of immunogenetic profiling for risk prediction and personalized strategies in oncology pharmacy practice.
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