The genetic underpinnings of anthracycline-induced cardiomyopathy predisposition

Clin Genet. 2021 Aug;100(2):132-143. doi: 10.1111/cge.13968. Epub 2021 May 2.

Abstract

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.

Keywords: SNPs; anthracyclines; cancer; cardiotoxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism
  • Anthracyclines / adverse effects*
  • Antibiotics, Antineoplastic / adverse effects
  • Cardiomyopathies / chemically induced*
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Cardiotoxicity / genetics
  • Genetic Predisposition to Disease*
  • Humans
  • NADPH Oxidases / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Organic Anion Transport Protein 1 / genetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Organic Anion Transport Protein 1
  • SLC22A6 protein, human
  • multidrug resistance protein 3
  • Alcohol Oxidoreductases
  • CBR3 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • NADPH Oxidases
  • NCF4 protein, human