Table 1.
Susceptibility genes in chemotherapy-induced cardiotoxicity.
| Study | Drug used | Type of cancer examined | Gene | SNP ID/location of pathogenic mutation | Targets | Cardiac toxicity | References |
|---|---|---|---|---|---|---|---|
| Rossi et al. (2009) | Doxorubicin | Large B-cell lymphoma | CYBA GSTA1 NCF4 |
rs4673 rs3957357 rs1883112 |
NAD(P)H oxidase, p40phox | EF decreased, echocardiography abnormalities, electrocardiogram abnormalities | [32] |
| Wojnowski et al. (2005) | Doxorubicin | Non-Hodgkin's lymphoma | NCF4 His72Tyr 7508T3A Gly671Val Val1188Glu Cys1515Tyr |
rs1883112 rs4673 rs1305833 rs8187694 rs8187710 |
NAD(P)H oxidase, p22phox | Arrhythmia, myocarditis-pericarditis, acute HF | [35] |
| Armenian et al. (2013) | Anthracyclines | Hematopoietic cell transplantation | RAC2 HFE | rs8187710 rs13058338 rs1799945 |
NAD(P)H oxidase | CHF, depressed EF or SF | [38] |
| Reichwagen et al. (2015) | Anthracyclines | CD20+ B-cell lymphomas | RAC2 CYBA |
rs13058338 rs4673 |
NADPH oxidase | Arrhythmia, reduced EF, ischemia | [40] |
| Sági et al. (2018) | Anthracyclines | ALL, OSC | CYP3A5 SLC28A3 ABCC2 NQO1 SLC22A6 |
rs4646450 rs7853758 rs3740066 rs1043470 rs6591722 |
ROS | LV function, SF, EF | [41] |
| Semsei et al. (2012) | Anthracyclines | ALL | ABCC1 | rs3743527 | ROS | LV dysfunction, reduced LVFS | [45] |
| Visscher et al. (2013) | Anthracyclines | Childhood cancer | UGT1A6 SLC28A3 |
rs17863783 rs7853758 rs885004 |
No report | SF < 26% | [46] |
| Visscher et al. (2012) | Anthracyclines | Childhood cancer | SLC28A3 | rs7853758 | No report | CHF, SF < 26% | [47] |
| Windsor et al. (2012) | Methotrexate | Malignant bone tumor | ABCC2 GSTP1 |
No report | ROS | Cardiac dysfunction, EF decreased | [48] |
| Hertz et al. (2016) | Doxorubicin | Breast cancer | ABCB1 CBR3 |
No report | Metabolism | EF < 55% | [50] |
| Lubieniecka et al. (2013) | Anthracyclines | AML | POR | rs2868177 rs13240755 |
ROS | LVEF decreased | [55] |
| Huang et al. (2017) | Daunorubicin | ALL | CYP3A5 (POR) | No report | Cytochrome P450 family 3 | Cardiac dysfunction | [56] |
| Vivenza et al. (2013) | Anthracyclines | Breast cancer | GSTM1 | No report | Oxidative/electrophilic species | Congestive HF, LVEF | [65] |
| Rajić et al. (2009) | Anthracyclines | ALL | CAT GSTT1 GSTM1 |
rs10836235 | ROS, SOD | Cardiac damage | [71] |
| Ruiz-Pinto et al. (2018) | Anthracyclines | Breast cancer | ETFB | rs79338777 | Mitochondrial dysfunction | Myocardial injury, LVEF decreased | [74] |
| Shizukuda et al. (2005) | Doxorubicin | No report | p53 | No report | ROS, Cu/Zn, SOD | Cardiac injury, LV systolic dysfunction | [77] |
| Wang et al. (2014) | Anthracyclines | Children's oncology | HAS3 gene | rs2232228 | ROS | LV dysfunction, EF < 40%, and FS < 28% | [79] |
| Visscher et al. (2015) | Anthracyclines | Childhood cancer | SLC22A17 SLC22A7 |
rs4982753 rs4149178 |
ROS, SOD | LV dysfunction | [83] |
| An et al. (2017) | Doxorubicin | Intermittent fasting | UVRAG | No report | LC3 II and p62 protein | Cardiac dysfunction | [101] |
| Wang et al. (2018) | Doxorubicin | No report | GCN2 | No report | Bcl-2, Bax, ATF4, UCP2 | LV dysfunction | [103] |
| McCaffrey et al. (2013) | Doxorubicin | Breast cancer | TCL1A MDR1 |
rs11849538 | PI3K, AKT, cIAP2, IAP-C, MIHC | Congestive HF, EF < 40%, LV dysfunction | [106] |
| Todorova et al. (2017) | Doxorubicin | Breast cancer | HLA | rs9264942 rs2523619 rs10484554 |
Inflammation, autoimmune disorders | Cardiac dysfunction, LVEF decline | [111] |
| Mori et al. (2010) | Doxorubicin | No report | Spp1 Fhl1 Timp1 Ccl7 Reg3b |
No report | Degeneration of myocardium and inflammation | Cardiac injury | [112] |
| Pop-Moldovan et al. (2017) | Doxorubicin | Hematological malignancies | TLR2 TLR4 |
No report | TLR | Diastolic dysfunction, LVEF decreased | [118] |
| Li et al. (2018) | Doxorubicin | Mammary tumor | TLR9 | No report | PI3Kγ | Myocardial dysfunction | [120] |
| Todorova et al. (2017) | Doxorubicin | Breast cancer | MicroRNA | No report | IL-17, TNF-α, NF-κB | Cardiac dysfunction, LVEF declined | [129] |
| Zhao et al. (2014) | Bevacizumab | Colorectal cancer | miRNA1254 | No report | CRP, MMPs | CHF | [132] |
| Yin et al. (2016) | Doxorubicin | No report | miR-320a | No report | VEGF | Cardiac dysfunction | [135] |
| Zhu et al. (2017) | Doxorubicin | DLBCL | miR-34a | No report | Caspase-3, Bcl-2 | Cardiac dysfunction | [136] |
| Cascales et al. (2012) | Doxorubicin | Hematological | C282Y-Y H63D-H |
No report | Iron metabolism disorder | HF, LVEF decrease | [142] |
| Lipshultz et al. (2013) | Doxorubicin | ALL | C282Y | No report | Iron metabolism disorder | Cardiac dysfunction, LVEF, cTnT, NT-proBNP | [144] |
| Ichikawa et al. (2014) | Doxorubicin | No report | ABCB8 | No report | Mitochondrial iron | Cardiomyopathy | [146] |
| Fang et al. (2019) | Doxorubicin | No report | Hmox1 | No report | Mitochondrial iron | Cardiomyopathy | [151] |
| Blanco et al. (2008) | Anthracyclines | Childhood cancer | CBR3 V244M |
No report | Metabolism | CHF | [155] |
| Reinbolt et al. (2016) | Adriamycin, cytoxan | Breast cancer | CBR1 CBR3 |
No report | Metabolism | EF < 50% and >15% | [156] |
| Salanci et al. (2012) | Anthracyclines | No report | CBR3 GSTP1 |
No report | Metabolism | Cardiac dysfunction, LVEFs < 50% | [157] |
| Blanco et al. (2012) | Anthracyclines | Childhood cancer | CBRs | No report | Metabolism | Cardiomyopathy, EF < 40%, SF < 28% | [158] |
| Lubieniecka et al. (2012) | Anthracyclines | AML | AKR CBR |
No report | Metabolism | LVEF% drop | [162] |
| Wasielewski et al. (2014) | Anthracyclines | Adult and childhood cancer | MYH7 | No report | Sarcomere disruption | Dilated cardiomyopathy | [166] |
| Wang et al. (2016) | Anthracyclines | Children oncology | CELF4 | rs1786814 | Sarcomere disruption | Cardiomyopathy | [171] |
| Garcia-Pavia et al. (2019) | Anthracyclines | Multiple cancers | TTNtv | No report | Sarcomere disruption | Dilated cardiomyopathy | [179] |
| Ferreira et al. (2017) | Doxorubicin | No report | DNA methylation | No report | Epigenetic | Decreased mtDNA levels | [183] |
| Ferreira et al. (2019) | Doxorubicin | No report | DNMT1 | No report | Epigenetic | Upregulation of mtDNA transcripts | [185] |
| Beauclair et al. (2007) | Trastuzumab | Breast cancer | Her2 | No report | No report | LVEF decreased | [186] |
| Stanton et al. (2015) | Trastuzumab | Breast cancer | Ile 655 Val Pro 1170 Ala |
rs1058808 rs1136201 |
No report | CHF, LVEF < 50% | [188] |
| Peña et al. (2015) | Trastuzumab | Breast cancer | HER2 655 A>G |
rs1136201 | No report | CHF, LVEF < 50% | [189] |
| Roca et al. (2013) | Trastuzumab | Breast cancer | HER2 Ile655Val | No report | MAPK and PI3 K/Akt | CHF, LVEF < 50% | [190] |
| Ruiz-Pinto et al. (2017) | Anthracyclines | Pediatric cancer | GPR35 | rs12468485 | No report | LV dysfunction, SF < 26% | [196] |
| Sachidanandam et al. (2012) | Doxorubicin | Childhood cancer | HNMT | rs17583889 | No report | SF < 26% | [199] |
| Salata et al. (2013) | Chemotherapy Radiotherapy |
Breast cancer | RAS-related genes | No report | AT1 receptor | Cardiac remodeling | [203] |
| Schneider et al. (2017) | Anthracyclines | Breast cancer | SNP | rs28714259 | No report | CHF, LVEF < 50%, acute coronary syndrome, supraventricular tachycardia, myocardial dysfunction | [205] |
| Kitagawa et al. (2012) | Epirubicin Cyclophosphamide 5-Fluorouracil |
Breast cancer | FEC100 | No report | No report | Arrhythmias, QTc interval prolongation | [208] |