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Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury

Nephrotoxicity is a common and dose-limiting side effect of platinum compounds, which often manifests as acute kidney injury or hypomagnesemia. This study aimed to investigate the genetic risk loci for platinum-induced nephrotoxicity. Platinum-treated brain tumor and head–neck tumor patients were ge...

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Autores principales: Klumpers, Marije J., Witte, Ward De, Gattuso, Giovanna, Schiavello, Elisabetta, Terenziani, Monica, Massimino, Maura, Gidding, Corrie E. M., Vermeulen, Sita H., Driessen, Chantal M., van Herpen, Carla M., van Meerten, Esther, Guchelaar, Henk-Jan, Coenen, Marieke J. H., te Loo, D. Maroeska W. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224783/
https://www.ncbi.nlm.nih.gov/pubmed/35743677
http://dx.doi.org/10.3390/jpm12060892
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author Klumpers, Marije J.
Witte, Ward De
Gattuso, Giovanna
Schiavello, Elisabetta
Terenziani, Monica
Massimino, Maura
Gidding, Corrie E. M.
Vermeulen, Sita H.
Driessen, Chantal M.
van Herpen, Carla M.
van Meerten, Esther
Guchelaar, Henk-Jan
Coenen, Marieke J. H.
te Loo, D. Maroeska W. M.
author_facet Klumpers, Marije J.
Witte, Ward De
Gattuso, Giovanna
Schiavello, Elisabetta
Terenziani, Monica
Massimino, Maura
Gidding, Corrie E. M.
Vermeulen, Sita H.
Driessen, Chantal M.
van Herpen, Carla M.
van Meerten, Esther
Guchelaar, Henk-Jan
Coenen, Marieke J. H.
te Loo, D. Maroeska W. M.
author_sort Klumpers, Marije J.
collection PubMed
description Nephrotoxicity is a common and dose-limiting side effect of platinum compounds, which often manifests as acute kidney injury or hypomagnesemia. This study aimed to investigate the genetic risk loci for platinum-induced nephrotoxicity. Platinum-treated brain tumor and head–neck tumor patients were genotyped with genome-wide coverage. The data regarding the patient and treatment characteristics and the laboratory results reflecting the nephrotoxicity during and after the platinum treatment were collected from the medical records. Linear and logistic regression analyses were performed to investigate the associations between the genetic variants and the acute kidney injury and hypomagnesemia phenotypes. A cohort of 195 platinum-treated patients was included, and 9,799,032 DNA variants passed the quality control. An association was identified between RBMS3 rs10663797 and acute kidney injury (coefficient −0.10 (95% confidence interval −0.13–−0.06), p-value 2.72 × 10(−8)). The patients who carried an AC deletion at this locus had statistically significantly lower glomerular filtration rates after platinum treatment. Previously reported associations, such as BACH2 rs4388268, could not be replicated in this study’s cohort. No statistically significant associations were identified for platinum-induced hypomagnesemia. The genetic variant in RBMS3 was not previously linked to nephrotoxicity or related traits. The validation of this study’s results in independent cohorts is needed to confirm this novel association.
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spelling pubmed-92247832022-06-24 Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury Klumpers, Marije J. Witte, Ward De Gattuso, Giovanna Schiavello, Elisabetta Terenziani, Monica Massimino, Maura Gidding, Corrie E. M. Vermeulen, Sita H. Driessen, Chantal M. van Herpen, Carla M. van Meerten, Esther Guchelaar, Henk-Jan Coenen, Marieke J. H. te Loo, D. Maroeska W. M. J Pers Med Article Nephrotoxicity is a common and dose-limiting side effect of platinum compounds, which often manifests as acute kidney injury or hypomagnesemia. This study aimed to investigate the genetic risk loci for platinum-induced nephrotoxicity. Platinum-treated brain tumor and head–neck tumor patients were genotyped with genome-wide coverage. The data regarding the patient and treatment characteristics and the laboratory results reflecting the nephrotoxicity during and after the platinum treatment were collected from the medical records. Linear and logistic regression analyses were performed to investigate the associations between the genetic variants and the acute kidney injury and hypomagnesemia phenotypes. A cohort of 195 platinum-treated patients was included, and 9,799,032 DNA variants passed the quality control. An association was identified between RBMS3 rs10663797 and acute kidney injury (coefficient −0.10 (95% confidence interval −0.13–−0.06), p-value 2.72 × 10(−8)). The patients who carried an AC deletion at this locus had statistically significantly lower glomerular filtration rates after platinum treatment. Previously reported associations, such as BACH2 rs4388268, could not be replicated in this study’s cohort. No statistically significant associations were identified for platinum-induced hypomagnesemia. The genetic variant in RBMS3 was not previously linked to nephrotoxicity or related traits. The validation of this study’s results in independent cohorts is needed to confirm this novel association. MDPI 2022-05-28 /pmc/articles/PMC9224783/ /pubmed/35743677 http://dx.doi.org/10.3390/jpm12060892 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Klumpers, Marije J.
Witte, Ward De
Gattuso, Giovanna
Schiavello, Elisabetta
Terenziani, Monica
Massimino, Maura
Gidding, Corrie E. M.
Vermeulen, Sita H.
Driessen, Chantal M.
van Herpen, Carla M.
van Meerten, Esther
Guchelaar, Henk-Jan
Coenen, Marieke J. H.
te Loo, D. Maroeska W. M.
Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
title Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
title_full Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
title_fullStr Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
title_full_unstemmed Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
title_short Genome-Wide Analyses of Nephrotoxicity in Platinum-Treated Cancer Patients Identify Association with Genetic Variant in RBMS3 and Acute Kidney Injury
title_sort genome-wide analyses of nephrotoxicity in platinum-treated cancer patients identify association with genetic variant in rbms3 and acute kidney injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224783/
https://www.ncbi.nlm.nih.gov/pubmed/35743677
http://dx.doi.org/10.3390/jpm12060892
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