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

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 polymorphis...

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Autores principales: Agema, Bram C., Koolen, Stijn L.W., de With, Mirjam, van Doorn, Nadia, Heersche, Niels, Oomen-de Hoop, Esther, Visser, Sabine, Aerts, Joachim G.J.V., Bins, Sander, van Schaik, Ron H.N., Mathijssen, Ron H.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230333/
https://www.ncbi.nlm.nih.gov/pubmed/32230800
http://dx.doi.org/10.3390/genes11040358
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author Agema, Bram C.
Koolen, Stijn L.W.
de With, Mirjam
van Doorn, Nadia
Heersche, Niels
Oomen-de Hoop, Esther
Visser, Sabine
Aerts, Joachim G.J.V.
Bins, Sander
van Schaik, Ron H.N.
Mathijssen, Ron H.J.
author_facet Agema, Bram C.
Koolen, Stijn L.W.
de With, Mirjam
van Doorn, Nadia
Heersche, Niels
Oomen-de Hoop, Esther
Visser, Sabine
Aerts, Joachim G.J.V.
Bins, Sander
van Schaik, Ron H.N.
Mathijssen, Ron H.J.
author_sort Agema, Bram C.
collection PubMed
description 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.
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spelling pubmed-72303332020-05-22 Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients Agema, Bram C. Koolen, Stijn L.W. de With, Mirjam van Doorn, Nadia Heersche, Niels Oomen-de Hoop, Esther Visser, Sabine Aerts, Joachim G.J.V. Bins, Sander van Schaik, Ron H.N. Mathijssen, Ron H.J. Genes (Basel) Article 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. MDPI 2020-03-27 /pmc/articles/PMC7230333/ /pubmed/32230800 http://dx.doi.org/10.3390/genes11040358 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Agema, Bram C.
Koolen, Stijn L.W.
de With, Mirjam
van Doorn, Nadia
Heersche, Niels
Oomen-de Hoop, Esther
Visser, Sabine
Aerts, Joachim G.J.V.
Bins, Sander
van Schaik, Ron H.N.
Mathijssen, Ron H.J.
Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients
title Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients
title_full Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients
title_fullStr Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients
title_full_unstemmed Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients
title_short Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients
title_sort influence of genetic variation in comt on cisplatin-induced nephrotoxicity in cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230333/
https://www.ncbi.nlm.nih.gov/pubmed/32230800
http://dx.doi.org/10.3390/genes11040358
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