The genetic underpinnings of anthracycline‐induced cardiomyopathy predisposition

Anthracyclines, chemotherapeutic agents that have contributed to significant improvements in cancer survival, also carry risk of both acute and chronic cardiotoxicity. This has led to significantly elevated risks of cardiac morbidity and mortality among cancer survivors treated with these agents. Certain treatment related, demographic, and medical factors increase an individual's risk of anthracycline induced cardiotoxicity; however, significant variability among those affected suggests that there is an underlying genetic predisposition to anthracycline induced cardiotoxicity. The current narrative review seeks to summarize the literature to date that has identified genetic variants associated with anthracycline induced cardiotoxicity. These include variants found in genes that encode proteins associated with anthracycline transportation and metabolism, those that encode proteins associated with the generation of reactive oxygen species, and those known to be associated with cardiac disease. While there is strong evidence that susceptibility to anthracycline induced cardiotoxicity has genetic underpinnings, the majority of work to date has been candidate gene analyses. Future work should focus on genome-wide analyses including genome-wide association and sequencing-based studies to confirm and expand these findings.