Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients

Genes

RonH.N. van Schaik¹  BramC. Agema¹  Mirjam de With¹  StijnL.W. Koolen²  Esther Oomen-de Hoop²  Nadia van Doorn²  Niels Heersche²  RonH.J. Mathijssen²  Sander Bins²  Sabine Visser³  JoachimG.J.V. Aerts³ 

[1] Department of Clinical Chemistry, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands;Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands;Department of Pulmonology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands;

关键词: cisplatin;    acute kidney injury;    COMT;    nephrotoxicity;    SNP;   

DOI  :  10.3390/genes11040358

来源: DOAJ

【 摘 要 】

Cisplatin is a chemotherapeutic agent widely used for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin, dose-limiting acute kidney injury (AKI) occurs. Here, we assessed the association of 3 catechol-O-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) with increased cisplatin-induced nephrotoxicity. In total, 551 patients were genotyped for the 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316), and c.616–367 C>T (rs9332377) polymorphisms. Associations between these variants and AKI grade ≥3 were studied. The presence of a homozygous variant of c.616-367C>T was associated with a decreased occurrence of AKI grade 3 toxicity (p = 0.014, odds ratio (OR) 0.201, 95% confidence interval (CI) (0.047–0.861)). However, we could not exclude the role of dehydration as a potential cause of AKI in 25 of the 27 patients with AKI grade 3, which potentially affected the results substantially. As a result of the low incidence of AKI grade 3 in this dataset, the lack of patients with a COMT variant, and the high number of patients with dehydration, the association between COMT variants and AKI does not seem clinically relevant.

【 授权许可】

Unknown