1. ¹Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany
2. ²Department of Phoniatrics and Pediatric Audiology, University Hospital of Muenster, Muenster, Germany

Correspondence: Professor Dr med. A. am Zehnhoff-Dinnesen, University Hospital of Muenster, Department of Phoniatrics and Pediatric Audiology, Kardinal-von-Galen-Ring 10, 48149 Münster, Germany. E-mail: A.am.Zehnhoff.Dinnesen@uni-muenster.de

³Both these authors contributed equally to this work.

Received 9 October 2006; Revised 18 January 2007; Accepted 21 March 2007; Published online 24 April 2007.

Abstract

Ototoxicity and nephrotoxicity are dose-limiting side effects of cisplatin. Megalin, a member of the low-density lipoprotein receptor family, is highly expressed in renal proximal tubular cells and marginal cells of the stria vascularis of the inner ear – tissues, which accumulate high levels of platinum–DNA adducts. On the assumption that the mechanisms of cisplatin-induced nephro- and ototoxicity involve megalin we analyzed the incidence of the non-synonymous single nucleotide polymorphisms (SNP) rs2075252 and rs4668123 in 25 patients who developed a distinct hearing loss during cisplatin therapy and in 25 patients without hearing impairment after cisplatin therapy. We found no association between cisplatin-induced ototoxicity and any allele of rs4668123 but observed a higher frequency of the A-allele of rs2075252 in the group with hearing impairment than in the group with normal hearing after cisplatin therapy (0.32 versus 0.14) (²=5.83, P<0.02; odds ratio: 3.45; 95% confidence interval: 1.11–11.2) indicating that SNPs at the megalin gene might impact the individual susceptibility against cisplatin-induced ototoxicity.