Format

Send to

Choose Destination
Pharmacogenomics. 2015;16(10):1065-76. doi: 10.2217/pgs.15.61. Epub 2015 Jul 31.

Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children.

Author information

1
Centre for Molecular Medicine & Therapeutics, Child & Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada.
2
Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
3
Division of Pediatric Cardiology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
4
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
5
Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
6
Department of Paediatrics, Children's Hospital/London Health Sciences Centre, London, ON, Canada.
7
Division of Translational Therapeutics, Department of Pediatrics, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.

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.

KEYWORDS:

anthracyclines; association study; cardiotoxicity; childhood cancer; pharmacogenomics

PMID:
26230641
DOI:
10.2217/pgs.15.61
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center