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.

Acute kidney injury, Cisplatin, COMT, Nephrotoxicity, SNP
dx.doi.org/10.3390/genes11040358, hdl.handle.net/1765/126078
Genes
Department of Clinical Chemistry

Agema, B.C. (Bram C.), Koolen, S.L.W, de With, M. (Mirjam), van Doorn, N. (Nadia), Heersche, N. (Niels), Oomen - de Hoop, E, … Mathijssen, A.H.J. (2020). Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients. Genes, 11(4). doi:10.3390/genes11040358