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,
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