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The anticancer anthracyclines doxorubicin and daunorubicin  are used to treat a variety of cancers in dogs. The therapeutic utility of  anthracyclines is limited by cardiotoxicity in some cases. Synthesis of  anthracycline alcohol metabolites by carbonyl reductase 1 (CBR1) is crucial for  the pathogenesis of cardiotoxicity. We hypothesize that genetic polymorphisms  in canine cbr1 contribute to the variable pharmacodynamics of  anthracyclines in dogs. DNA sequence variants in canine cbr1 were  investigated in DNA samples from dogs of seven breeds. Thirteen SNPs were  detected in canine cbr1. A 10-bp deletion in the 5'-untranslated region  (5'-UTR) was found in specimens from the Labrador Retriever, Beagle, Siberian  Husky, and Boxer breeds. The 5'-UTR also included a polymorphic "hot spot"  region immediately downstream of the 10-bp deletion. DNA sequence variants in  the "hot spot region" ranged from 1 to 21 bp in length. Bioinformatics searches  identified a cluster of three to six potential binding sites for the  transcription factor Sp1 in the DNA segment containing both the "hot spot"  region and the 10-bp deletion. This information provides a foundation to allow  us to investigate whether DNA sequence variants in the 5'-UTR of canine cbr1 impact the pharmacodynamics of anticancer anthracyclines in dogs.

Short Communication DNA sequence variants in the carbonyl reductase 1 (cbr1) gene in seven breeds of Canis lupus familiaris