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

Journal of Personalized Medicine

Sita H. Vermeulen¹  Henk-Jan Guchelaar²  Marieke J. H. Coenen³  Ward De Witte³  Esther Van Meerten⁴  Carla M. Van Herpen⁵  Chantal M. Driessen⁵  Marije J. Klumpers⁶  D. Maroeska W. M. Te Loo⁶  Maura Massimino⁷  Giovanna Gattuso⁷  Elisabetta Schiavello⁷  Monica Terenziani⁷  Corrie E. M. Gidding⁸ 

[1] Department for Health Evidence, Radboud University Medical Center, Postbox 9101, 6500 HB Nijmegen, The Netherlands;Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Postbox 9600, 2300 RC Leiden, The Netherlands;Department of Human Genetics, Radboud University Medical Center, Postbox 9101, 6500 HB Nijmegen, The Netherlands;Department of Medical Oncology, Erasmus MC Cancer Institute, Postbox 2040, 3000 CA Rotterdam, The Netherlands;Department of Medical Oncology, Radboud University Medical Center, Postbox 9101, 6500 HB Nijmegen, The Netherlands;Department of Pediatrics, Radboud University Medical Center, Postbox 9101, 6500 HB Nijmegen, The Netherlands;Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy;Princess Maxima Center for Pediatric Oncology, Postbox 113, 3720 AC Bilthoven, The Netherlands;

关键词: cisplatin;    carboplatin;    nephrotoxicity;    acute kidney injury;    hypomagnesemia;    GWAS;   

DOI  :  10.3390/jpm12060892

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown