Pharmacogenetics of drug-induced ototoxicity caused by aminoglycosides and cisplatin

Aminoglycosides and the anticancer drug cisplatin can cause permanent hearing loss, which impacts patients' quality of life and results in considerable subsequent costs. Since patients' individual susceptibility to aminoglycoside- and cisplatin-induced ototoxicity varies considerably, strategies are needed to identify patients at risk, who may require alternative treatments or specific protection strategies. For both drugs, various genetic variants were linked to an increased or decreased risk for ototoxicity. Except for the association between the A1555G mitochondrial DNA mutation and aminoglycoside ototoxicity, their evidence is considered low because study cohorts were often small and replication studies either missing or contradictory. This review summarizes the pharmacogenetic markers linked to aminoglycoside- or cisplatin-induced ototoxicity and discusses reasons for replication failure and future perspective.