Unexpected doxorubicin-mediated cardiotoxicity in sisters: possible role of polymorphisms in histamine n-methyl transferase.

The anthracycline anticancer agent doxorubicin has long been recognized to induce a dose-limiting cardiotoxicity and may be associated with genes relevant to doxorubicin disposition. Recent reports suggest a role for a number of single nucleotide polymorphisms in anthracycline cardiotoxicity in children. We describe two adult sisters with anthracycline cardiotoxicity that developed after a relatively low dose of doxorubicin. One sister carried the variant genotype for histamine N-ethyl transferase (HNMT, rs17583889) while the other was heterozygous, suggesting a similar role for these genotypes in adults with anthracycline cardiotoxicity. Although this requires further study, these genotypes may be important in the clinical dosing, or use of the liposomal formulation of doxorubicin.