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.
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 cancerpatients 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.
Authors: Anke H Maitland-van der Zee; Bruce C Carleton; Zulfan Zazuli; Catharina J P Op 't Hoog; Susanne J H Vijverberg; Rosalinde Masereeuw; Shahrad Rod Rassekh; Mara Medeiros; Rodolfo Rivas-Ruiz Journal: Pediatr Nephrol Date: 2022-06-24 Impact factor: 3.714
Authors: Matthew R Trendowski; Omar El Charif; Paul C Dinh; Lois B Travis; M Eileen Dolan Journal: Clin Cancer Res Date: 2018-10-10 Impact factor: 12.531