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; Amstutz, Ursula; Canadian Pharmacogenomics Network for Drug Safety consortium, CPNDS (2015). Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children. Pharmacogenomics, 16(10), pp. 1065-1076. Future Medicine 10.2217/pgs.15.61
Full text not available from this repository. (Request a copy)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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry |
UniBE Contributor: |
Amstutz, Ursula |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1462-2416 |
Publisher: |
Future Medicine |
Language: |
English |
Submitter: |
Ursula Amstutz |
Date Deposited: |
04 Nov 2015 08:42 |
Last Modified: |
05 Dec 2022 14:49 |
Publisher DOI: |
10.2217/pgs.15.61 |
PubMed ID: |
26230641 |
Uncontrolled Keywords: |
anthracyclines; association study; cardiotoxicity; childhood cancer; pharmacogenomics |
URI: |
https://boris.unibe.ch/id/eprint/72420 |
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