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

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

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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:

04 Nov 2015 08:42

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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