Clemens, EvaEvaClemensBroer, LindaLindaBroerLanger, ThorstenThorstenLangerUitterlinden, André GAndré GUitterlindende Vries, Andrica C HAndrica C Hde Vriesvan Grotel, MartineMartinevan GrotelPluijm, Saskia F MSaskia F MPluijmBinder, HaraldHaraldBinderByrne, JulianneJulianneByrneBroeder, Eline van Dulmen-denEline van Dulmen-denBroederCrocco, MarcoMarcoCroccoGrabow, DesireeDesireeGrabowKaatsch, PeterPeterKaatschKaiser, MelanieMelanieKaiserKenborg, LineLineKenborgWinther, Jeanette FJeanette FWintherRechnitzer, CatherineCatherineRechnitzerHasle, HenrikHenrikHasleKepak, TomasTomasKepakvan der Kooi, Anne-Lotte FAnne-Lotte Fvan der KooiKremer, Leontien CLeontien CKremerKruseova, JarmilaJarmilaKruseovaKühni, ClaudiaClaudiaKühnivan der Pal, HeleenHeleenvan der PalParfitt, RossRossParfittDeuster, DirkDirkDeusterMatulat, PeterPeterMatulatSpix, ClaudiaClaudiaSpixTillmanns, AmelieAmelieTillmannsTissing, Wim J EWim J ETissingMaier, LaraLaraMaierAm Zehnhoff-Dinnesen, AntoinetteAntoinetteAm Zehnhoff-DinnesenZolk, OliverOliverZolkvan den Heuvel-Eibrink, Marry MMarry Mvan den Heuvel-Eibrink2024-10-282024-10-282020-04https://boris-portal.unibe.ch/handle/20.500.12422/182960Ototoxicity 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.en600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::360 - Social problems & social servicesarticle10.7892/boris.1345763166671410.1038/s41397-019-0113-1