Table 1.
PGx studies of anthracyclines cardiotoxicity (AIC) in breast cancer.
| Sample | Anthracycline (dose) | Follow-up (year) | Cardiotoxicity definition | Rational of gene selection | Studied Genes* | SNPs found to be significantly associated in multivariable analysis | Reference |
|---|---|---|---|---|---|---|---|
| 877 early BC patients | Epi (100 mg/m2) | Median 3.62 | - Asymptomatic decrease of LVEF > 10% - cardiac failure grade 3–5 |
-10 SNPs in 6 genes were previously found in association with AIC -11 SNPs related to treatment outcome |
ABCC1
ABCC2 CYBA NCF4 RAC2 SLC28A3 |
CT at rs246221 in ABCC1 is associated with LVEF decline >10%, (p=0.02) | (Vulsteke et al., 2015) |
| 166 BC patients suspected to have AIC | Dox (accumulative 240 mg/m2) | At least 12 months since receiving the anthracycline. | Systolic dysfunction defined by EF <55% | Variants previously reported to be associated with AIC or that had mechanistic rationale |
ABCB1
ABCB4 CBR3 CYP3A4 NCF4 RAC2 SLC28A3 TOP2B |
- rs1045642 in ABCB1
Has protective effect (p=0.049) - rs1056892 in CBR3 with increased risk of EF < 55% (p=0.002) |
(Hertz et al., 2016) |
| 162 BC patients | N/A | A retrospective study that collected data from 9 years span | Cardiomyopathy defined by a drop in EF to <50% or >15% decrease from pre-therapy and developing a new arrhythmia or MI after therapy | Genes in carbonyl reductase pathways |
CBR1
CBR3 |
No association was found in the studied SNPs | (Reinbolt et al., 2016) |
| 147 triple-negative BC patients | N/A | A retrospective study that collected data from 7 years span | Early-onset cardiac events (any change in the ECG following any of the first 4 cycles of therapy) | Selected SNPs related to autophagy |
ATG5
ATG7 ATG12 ATG13 ATM CASP3 CRYAB MAP1LC-3B STMN1 |
rs10838611 in ATG13 with early ECG abnormalities | (Liu et al., 2018) |
| 427 BC patients | Epi (100 mg/m2) | 12 months | Absolute decline in LVEF at least 10 points from baseline or to less than 53%, heart failure, coronary syndrome, or arrhythmias | The selected gene is involved in anthracyclines metabolism by glucuronidation | UGT2B7 | T allele UGT2B7 -161 with decreased risk of ACT (P = 0.004) |
(Li et al., 2019) |
AIC, anthracycline-induced cardiotoxicity; BC, breast cancer; Epi, epirubicin; Dox, doxorubicin; EF, ejection fraction; ECG, elecrtocardiography; LVEF, left ventricular ejection fraction.
*The mentioned genes were not fully covered in these studies, only specific polymorphisms in these genes were tested.