Department of Pediatrics, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina, USA.
Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Clin Genet. 2021 Aug;100(2):132-143. doi: 10.1111/cge.13968. Epub 2021 May 2.
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.
蒽环类药物是一种具有显著提高癌症存活率的化疗药物，但也有导致急性和慢性心脏毒性的风险。这导致接受这些药物治疗的癌症幸存者的心脏发病率和死亡率显著升高。某些与治疗相关的、人口统计学的和医学的因素会增加个体发生蒽环类药物引起的心脏毒性的风险；然而，受影响者之间存在显著的差异，这表明存在对蒽环类药物引起的心脏毒性的潜在遗传易感性。本综述旨在总结迄今为止已确定与蒽环类药物引起的心脏毒性相关的遗传变异的文献。这些变异包括编码与蒽环类药物转运和代谢相关的蛋白的基因中的变异、编码与活性氧生成相关的蛋白的基因中的变异，以及已知与心脏疾病相关的基因中的变异。虽然有强有力的证据表明蒽环类药物引起的心脏毒性易感性具有遗传基础，但迄今为止大多数工作都是候选基因分析。未来的工作应集中在全基因组分析上，包括全基因组关联和基于测序的研究，以确认和扩展这些发现。
