Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms. (October 2011)

• Record Type: Journal Article
• Authors: Tzvetkov, Mladen V; Behrens, Gerrit; O''Brien, Valerie P; Hohloch, Karin; Brockmöller, Jürgen; Benöhr, Peter
• Is Part Of: Pharmacogenomics. Volume 12:Number 10(2011)
• Page Start: 1417
• Page End: 1427
• Publication Date: 2011-10
• Subjects: cisplatin -- DNA repair -- ERCC1 -- nephrotoxicity -- OCT2 -- organic cation transporter -- polymorphisms; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.11.93
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: We investigated whether genetic polymorphisms may contribute to the interpatient variability of cisplatin-induced nephrotoxicity.Patients & methods: Polymorphisms in the candidate genes GSTM1, GSTT1, OCT1, OCT2, LARP2, ERCC1, XRCC1 and EPO were analyzed for associations with nephrotoxicity in 79 cancer patients receiving cisplatin-containing chemotherapy.Results: Higher cisplatin dose was associated with strongly decreased estimated glomerular filtration rates (eGFR) (r 2 = 0.205). Two highly genetically linked polymorphisms in the ERCC1 gene, 8092C>A and Asn118Asn, were significantly associated with change in eGFR, accounting for an additional 13% of interindividual variability. Homozygous carriers of the 8092A allele in ERCC1 showed no reduction in eGFR, compared with the 11.5% mean eGFR decrease in C allele carriers (p = 0.004). Homozygous carriers of the C allele of Asn118Asn showed no reduction in eGFR, compared with the 12.8% mean eGFR decrease seen in T allele carriers (p = 0.047). Polymorphisms in the other candidate genes were not associated with cisplatin-induced nephrotoxicity.Conclusion: Genetic polymorphisms in ERCC1 may be valuable predictors of cisplatin-induced nephrotoxicity. Original submitted 23 May 2011; Revision submitted 5 July 2011