Affiliation:
1. From the Department of Cardiology, Division of Heart & Lungs (M.L., A.J.T., M.J.C., F.W.A.) and Department of Medical Oncology (E.v.d.W.), University Medical Center Utrecht, University of Utrecht, The Netherlands; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht (F.W.A.); and Institute of Cardiovascular Science, Faculty of Population Health Sciences (F.W.A.) and Farr Institute of Health Informatics Research and Institute of Health Informatics (F.W.A.), University...
Abstract
Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment. We conducted a systematic literature search in PubMed and Embase, to identify studies investigating genetic risk factors for chemotherapy-related cardiac dysfunction. Included were articles describing genetic variants in humans altering susceptibility to chemotherapy-related cardiac dysfunction. The validity of identified studies was assessed by 10 criteria, including assessment of population stratification, statistical methodology, and replication of findings. We identified 40 studies: 34 exploring genetic risk factors for anthracycline-induced cardiotoxicity (n=9678) and 6 studies related to trastuzumab-associated cardiotoxicity (n=642). The majority (35/40) of studies had a candidate gene approach, whereas 5 genome-wide association studies have been performed. We identified 25 genetic variants in 20 genes and 2 intergenic variants reported significant at least once. The overall validity of studies was limited, with small cohorts, failure to assess population ancestry and lack of replication. SNPs with the most robust evidence up to this point are
CELF4
rs1786814 (sarcomere structure and function),
RARG
rs2229774 (topoisomerase-2β expression),
SLC28A3
rs7853758 (drug transport),
UGT1A6
rs17863783 (drug metabolism), and 1 intergenic variant (rs28714259). Existing evidence supports the hypothesis that genetic variation contributes to chemotherapy-related cardiac dysfunction. Although many variants identified by this systematic review show potential to improve risk stratification, future studies are necessary for validation and assessment of their value in a diagnostic and prognostic setting.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
61 articles.
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