Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Leong, Siew Lian; Chaiyakunapruk, Nathorn; Lee, Shaun Wen Huey

doi:10.1038/s41598-017-00075-1

Cited by 80 publications

(71 citation statements)

References 63 publications

(224 reference statements)

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“…Leong et al indicated that several polymorphisms of pharmacogenetics candidates across the anthracyclines biochemistry and cardiomyopathy pathways are potentially a predictor for anthracycline‐induced cardiotoxicity. However, the evidence is limited and further studies are needed to generate robust genetic predictor(s) …”

Section: Strategies For Preventionmentioning

confidence: 99%

Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity

Corremans

Adão

Keulenaer

et al. 2018

Clin Exp Pharma Physio

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Summary Anthracycline chemotherapy has a prominent role in treating many forms of cancer. Unfortunately, cardiotoxic side effects represent a serious limitation to their use, with doxorubicin being the leading drug of the group. Indeed, anthracycline‐induced cardiomyopathy is an important public health concern because it may not be detected for many years and remains a lifelong threat. Even after decades of investigation, neither the exact mode of action of anthracyclines nor the pathways leading to their side effect are fully understood. It is increasingly important to establish collaboration between oncologists and cardiologists to improve the management of cancer patient receiving anthracyclines. This article reviews the clinical course, pathogenesis, cardiac monitoring and new concepts in diagnosing and preventing anthracycline‐induced cardiotoxicity.

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Section: Strategies For Preventionmentioning

confidence: 99%

Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity

Corremans

Adão

Keulenaer

et al. 2018

Clin Exp Pharma Physio

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“…Overall, most candidate gene studies are limited by small patient numbers, lack of replication studies and functional data (66••). A systemic review of 28 candidate gene association studies examined 84 different genes and 147 single nucleotide polymorphisms [67]. Three risk variants in genes ABCC2 , CYBA , and RAC2 significantly increased the risk for anthracycline-induced cardiotoxicity.…”

Section: Studies Of Chemotherapy-induced Cardiotoxicity In Mice and Hmentioning

confidence: 99%

Pharmacogenetics of Chemotherapy-Induced Cardiotoxicity

Chang

Wang

2018

Curr Oncol Rep

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Most of the studies rely on in vitro cytotoxic assays. There have been several smaller scale candidate gene approaches and a handful of genome-wide studies linking genetic variation to susceptibility to chemotherapy-induced cardiotoxicity. Currently, pharmacogenomic testing of all childhood cancer patients with an indication for doxorubicin or daunorubicin therapy for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is recommended. There is no recommendation regarding testing in adults. There is clear evidence pointing to the role of pharmacogenetics and pharmacogenomics in cardiotoxicity susceptibility to chemotherapeutic agents. Larger scale studies are needed to further identify susceptibility markers and to develop pharmacogenomics-based risk profiling to improve quality of life and life expectancy in cancer survivors.

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“…The other mechanisms include the formation of toxic drug metabolites, inhibition of nucleotide and protein synthesis, release of vasoactive amines, suppression of specific gene expression, impairment of mitochondrial membrane binding, aggregation of creatine kinase activity, induction of apoptosis, interference of intracellular calcium homeostasis, changes in respiratory chain proteins, induction of nitric oxide synthase, enhancement of mitochondrial cytochrome C release, etc. [11,12]. Other studies have shown that anthracyclines can lead to myocardial cell damage, inducing cardiac mitochondrial diseases and impairment of mitochondrial DNA and the respiratory chain in chronic cardiomyopathy [13][14][15].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

Wang¹,

Chen

Zhang³

et al. 2020

BMC Cardiovasc Disord

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Background: The current diagnostic methods and treatments still fail to lower the incidence of anthracyclineinduced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicityrelated abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Methods: Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapyinduced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. Result: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-β signaling pathway and adhesion signaling pathway. Conclusions: Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-β signaling pathway and adhesion signaling pathway.

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Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Cited by 80 publications

References 63 publications

Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity

Update on pathophysiology and preventive strategies of anthracycline‐induced cardiotoxicity

Pharmacogenetics of Chemotherapy-Induced Cardiotoxicity

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

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