顺铂常用于治疗实体肿瘤；然而，其使用可能会引起药物引起的听力损伤（即耳毒性）。某些遗传变异的存在与顺铂引起的耳毒性的发展/发生有关，表明遗传因素可能能够预测更容易发展耳毒性的患者。本文旨在回顾与顺铂引起的耳毒性相关的遗传关联，并讨论其临床相关性。根据加拿大药物基因组学网络药物安全项目的委托，基于2020年偏好报告项目 的系统回顾和Meta分析报告。包括报道遗传变异与顺铂引起的耳毒性间的关联的药物基因组学研究。总结和评价遗传关联的证据，并确定可用于指导未来药物基因组学研究的知识空白。总共评估了40个报告，涉及47个独立的患者群体，捕获了涉及24个基因的关联。根据GRADE标准，2个基因的遗传变异在顺铂引起的耳毒性预测上具有强大（即奥斯比比值≥3）和一致（即在≥3个独立群体中重复）的预测能力。具体来说，ACYP2变异体与儿童和成人的耳毒性相关，而TPMT变异体与儿童相关。还存在涉及其他几个基因的关联的鼓舞人心的证据；然而，还需要进一步的研究来确定潜在的临床相关性。ACYP2和TPMT的遗传变异可能有助于预测最高风险患者发展顺铂引起的耳毒性。需要进一步研究（包括考虑不同儿童和成人患者群体的重复研究）来确定是否其他基因的遗传变异可以进一步确定最易受风险患者。© 2023 Wolters Kluwer Health公司。保留所有权利。

Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.