The association between DNA repair genes polymorphisms and cisplatin-induced ototoxicity in cancer patients: a systematic review

Ototoxicity is a dose-limiting toxicity of cisplatin. Several DNA repair gene polymorphisms have been investigated for their association with cisplatin-induced ototoxicity (CIO), but their predictive value remains controversial. This systematic review evaluated genetic predisposition to CIO via DNA repair gene polymorphisms. PubMed, SCOPUS, Web of Science, trial registries, and gray literature sources were searched, and reference lists of included studies were screened. Study quality was assessed using the Q-Genie tool, and reporting followed PRISMA guidelines. The protocol was registered on PROSPERO (ID: CRD420251112849). Eight studies with 672 subjects were deemed eligible, investigating nine DNA repair genes (XPA, XPC, ERCC1, ERCC2, XRCC1, EX01, ERCC4, and ERCC5), covering 96 single-nucleotide polymorphisms (SNPs), 54 of which were in DNA repair pathways. AC+CC genotypes of XPC rs2228001 were associated with decreased risk of CIO (OR: 0.20, 95% CI: 0.06–0.70, p = 0.01). Conversely, combining XPC rs2228001 with SNPs in GSTP1, FASL, or MSH3 showed the highest risks (ORs of 32.22, 22.29, and 17.09). Although several DNA repair gene polymorphisms have been explored, findings remain inconsistent and limited by populations and SNPs studied. Larger, well-designed studies with standardized methodologies are needed to confirm these associations and identify genetic markers for predicting high-risk patients for CIO.