Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children
Publisher DOI
PubMed ID
26230641
Abstract
AIM
To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model.
PATIENTS & METHODS
Two cohorts treated for childhood cancer (n = 344 and 218, respectively) were genotyped for 4578 SNPs in drug ADME and toxicity genes.
RESULTS
Significant associations were identified in SLC22A17 (rs4982753; p = 0.0078) and SLC22A7 (rs4149178; p = 0.0034), with replication in the second cohort (p = 0.0071 and 0.047, respectively). Additional evidence was found for SULT2B1 and several genes related to oxidative stress. Adding the SLC22 variants to the prediction model improved its discriminative ability (AUC 0.78 vs 0.75 [p = 0.029]).
CONCLUSION
Two novel variants in SLC22A17 and SLC22A7 were significantly associated with anthracycline-induced cardiotoxicity and improved a genotype-guided risk prediction model, which could improve patient risk stratification.
To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model.
PATIENTS & METHODS
Two cohorts treated for childhood cancer (n = 344 and 218, respectively) were genotyped for 4578 SNPs in drug ADME and toxicity genes.
RESULTS
Significant associations were identified in SLC22A17 (rs4982753; p = 0.0078) and SLC22A7 (rs4149178; p = 0.0034), with replication in the second cohort (p = 0.0071 and 0.047, respectively). Additional evidence was found for SULT2B1 and several genes related to oxidative stress. Adding the SLC22 variants to the prediction model improved its discriminative ability (AUC 0.78 vs 0.75 [p = 0.029]).
CONCLUSION
Two novel variants in SLC22A17 and SLC22A7 were significantly associated with anthracycline-induced cardiotoxicity and improved a genotype-guided risk prediction model, which could improve patient risk stratification.
Date Issued
2015-07
Publication Type
Article
Subject(s)
Subjects
anthracyclines
•
association study
•
cardiotoxicity
•
childhood cancer
•
pharmacogenomics
Language(s)
en
Author(s)
Visscher, Henk | |
Rassekh, S Rod | |
Sandor, George S | |
Caron, Huib N | |
van Dalen, Elvira C | |
Kremer, Leontien C | |
van der Pal, Helena J | |
Rogers, Paul C | |
Rieder, Michael J | |
Carleton, Bruce C | |
Hayden, Michael R | |
Ross, Colin J | |
Canadian Pharmacogenomics Network for Drug Safety consortium, CPNDS |
Additional Credits
Journal
Pharmacogenomics
Publisher
Future Medicine
ISSN
1462-2416