TY - JOUR
T1 - Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients
AU - Agema, Bram C.
AU - Koolen, Stijn L.W.
AU - de With, Mirjam
AU - van Doorn, Nadia
AU - Heersche, Niels
AU - Oomen-De Hoop, Esther
AU - Visser, Sabine
AU - Aerts, Joachim G.J.V.
AU - Bins, Sander
AU - van Schaik, Ron H.N.
AU - Mathijssen, Ron H.J.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/3/27
Y1 - 2020/3/27
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85082791952
U2 - 10.3390/genes11040358
DO - 10.3390/genes11040358
M3 - Article
C2 - 32230800
SN - 2073-4425
VL - 11
JO - Genes
JF - Genes
IS - 4
M1 - 358
ER -
