The Pharmacogenomics of Cisplatin-Induced Ototoxicity

Cisplatin is a first line treatment for a wide range of cancers; one commonly observed adverse drug reaction (ADR) of cisplatin is ototoxicity. Onset of ototoxicity from cisplatin is inconsistent and no single risk factor can reliably predict whether a patient will develop ototoxicity. A genetic factor has been explored for these reasons. This study reviews and summarizes the strongest evidence toward a genetic association. A search of the literature was conducted across three databases for studies exploring the genetic association with cisplatin ototoxicity. 15 unique genes were observed by at least two unique studies with single nucleotide polymorphisms (SNPs), which significantly affected the likelihood of cisplatin-induced ototoxicity. There are many SNPs across a variety of genes that can significantly affect the likelihood of cisplatin-induced ototoxicity. Comparing the findings of studies is difficult because of significant heterogeneity in patient characteristics, treatment plans, and the classification of ototoxicity. Despite this, variants in ACYP2 (rs1872328), SLC22A2 (rs316019), and TLR4 (rs10759932) emerged as the most reproducible findings in this review.