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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7230333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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