Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8–21.5; P = 5.6 × 10⁻⁷) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m²: OR: 2.4; 95% CI: 1.3–4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04–14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07–2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

耳毒性是铂类治疗的常见副作用，表现为不可逆的高频感音神经性听力损失。遗传关联研究表明，SNPs在与顺铂或耳聋相关的基因中具有重要作用。在这项研究中，对接受顺铂治疗的429名儿科患者进行了10个候选SNP的基因分型。Logistic回归分析显示，治疗年龄更小（≤5岁vs> 15岁：OR：9.1； 95％CI：3.8–21.5；P  = 5.6×10 ^-7）和更高的顺铂累积剂量（> 450 vs≤300） mg / m ²：或：2.4; 95％CI：1.3–4.6; P = 0.007）会带来明显的耳毒性风险。在所研究的SNP中，没有一个与耳毒性的增加显着相关。在荟萃分析中，ACYP2 rs1872328（OR：3.94; 95％CI：1.04–14.03; P  = 0.04）和SLC22A2 rs316019（OR：1.46; 95％CI：1.07–2.00; P  = 0.02）与耳毒性相关。为了加深对SNP与耳毒性之间联系的理解，我们提出了一种多基因模型，该模型考虑了顺铂途径的多个相互作用基因，这些基因共同导致耳毒性的风险增加。