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Pharmacogenomics ; 16(4): 323-32, 2015.
Article in English | MEDLINE | ID: mdl-25823781

ABSTRACT

AIM: Assuming that genetic variants of the SLC22A2 and SLC31A1 transporter affect patients' susceptibility to cisplatin-induced ototoxicity, we compared the distribution of 11 SLC22A2 variants and the SLC31A1 variant rs10981694 between patients with and without cisplatin-induced ototoxicity. PATIENTS & METHODS: Genotyping was performed in 64 pediatric patients and significant findings were re-evaluated in 66 adults. RESULTS: The SLC22A2 polymorphism rs316019 (c.808G>T; Ser270Ala) was significantly associated with protection from cisplatin-induced ototoxicity in the pediatric (p = 0.022) and the adult cohort (p = 0.048; both: Fisher's exact test). This result was confirmed by multiple logistic regression analysis accounting for age which was identified as a relevant factor for ototoxicity as well (rs316019: OR [G/T vs G/G] = 0.12, p = 0.009; age: OR [per year]: 0.84, p = 0.02). CONCLUSION: These results identified rs316019 as potential pharmacogenomic marker for cisplatin-induced ototoxicity and point to a critical role of SLC22A2 for cisplatin transport in humans and its contribution to the organ specific side effects of this drug. Original submitted 17 September 2014; Revision submitted 19 December 2014.


Subject(s)
Cation Transport Proteins/genetics , Cisplatin/adverse effects , Neoplasms/drug therapy , Organic Cation Transport Proteins/genetics , Adolescent , Adult , Child , Child, Preschool , Cisplatin/administration & dosage , Copper Transporter 1 , Drug-Related Side Effects and Adverse Reactions/genetics , Female , Genetic Association Studies , Genotype , Haplotypes , Humans , Male , Neoplasms/genetics , Neoplasms/pathology , Organic Cation Transporter 2 , Polymorphism, Single Nucleotide
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