Table 3.
Selected SNPs previously reported to be associated with congestive heart failure
| Study | Number of Patients (sample size) | Study Set | Dose and Schedule of Anthracyclines | Phenotype | Genotype | Genes of top association | Validation with number of independent cohort |
|---|---|---|---|---|---|---|---|
| Wojnowski et al.1 | 450 | DSHNHL-B1/B2 | Doxorubicin/uniform dose & schedule | WHO grade 3 and 4 cardiotoxicity | Candidate SNPs in 82 genes in anthracycline pharmacodynamics | NADPH, BCC1, ABCC2 | No |
| Blanco et al.2 | 145 | Retrospective pediatric cohort | Any anthracycline/Variable dose & schedule | Self-reported symptoms | Candidate genes NQO1, CBR3 | CBR3 | No |
| Rajić V et al.3 | 76 | Retrospective pediatric cohort | Any anthracycline/variable dose & schedule | Cardiologist defined cardiac damage | Candidate SNPs in SOD2, CAT, GSTT1, GSTM1 | CAT | No |
| Blanco et al.4 | 487 | COG-ALTE03N1 | Any anthracycline/variable dose & schedule | AHA guidelines | Candidate SNPs in CBR3 and CBR1 | CBR3 | No |
| Semsei et al.5 | 235 | Retrospective pediatric cohort | Doxorubicin & Daunorubicin/uniform dose & schedule | Cardiac function measured by LVFS | Candidate SNPs in ABCC1 | ABCC1 | No |
| Visscher et al.6 | 156 | Retrospective pediatric cohort | Doxorubicin & Daunorubicin/Variable dose & schedule | CTCAE v3 | Candidate SNPs in 220 genes in anthracycline pharmacodynamics | CBR3, CB4, HMNT,ABCC1, LC28A3 | Yes-Two cohorts |
| Volkan-Salanci et al.7 | 70 | Prospective adult cohort | Doxorubicin/Variable dose & schedule | Various measures of cardiac function | Candidate SNPs in CBR3 and GSTP1 | CBR3, STP1 | Yes |
| Armenia et al.8 | 255 | Retrospective adult cohort | Any anthracycline/Variable dose & schedule | ACC/AHA guidelines | Candidate genes in anthracycline metabolism and pharmacodynamics | NADPH, HFE, ABCC2 | No |
| Lubieniecka et al.9 | 91 | Retrospective adult cohort | Daunorubicin/Variable dose & schedule | Acute cardiotoxicity, | 60 Candidate genes in anthracycline metabolism and efflux | POR | No |
| Sachidan andam et al.10 | 2 | Two adult sisters with CHF | Doxorubicin/Variable dose & schedule | Sister 1 - cardiac transplant. Sister 2 - LVEF dropped to 22% |
Candidate gene ABCC1, NADPH, CBR1, CBR3, HMNT and ABCB4 | HNMT | No |
| Wang et al.11 | 287 | COG-ALTE03N1 | Any anthracycline/Variable dose & schedule | AHA guidelines | 2100 Candidate genes on ITMAT/Broad CARe cardiovascular SNP array | HAS3 | Yes |
| Visscher et al.12 | 344 | Retrospective pediatric cohort | Doxorubicin & Daunorubicin/variable dose & schedule | CTCAE v3 | Candidate 4578 SNPs in drug pharmacokinetic and toxicity genes | SLC22A7, SLC22A17 | Yes |
| Aminkeng et al.13 | 280 | Retrospective pediatric cohort | Doxorubicin & Daunorubicin/Variable dose & schedule | CTCAE v3 | GWAS | RARG | Yes –Two cohorts |
| Schneider et al. (current study) | 102 | ECOG-5103 | Doxorubicin/Uniform dose & schedule | cardiologist adjudicated | GWAS | rs28714259 in intergenic region of chr 15 | Yes-Two cohorts |
ACC = American College of Cardiology; AHA =American Heart Association ; ALL= acute lymphoblastic leukemia; AML = Acute myeloid leukemia; CHF = Congestive Heart Failure; COG = Children’s Oncology Group; CTCAE = Common Terminology Criteria for Adverse Events; DSHNHL = German High-Grade Non-Hodgkin’s Lymphoma Study Group; ECG = Electrocardiogram; ECHO = Echocardiogram; ECOG = Eastern Cooperative Oncology Group; HCT = Hematopoietic cell transplantation; LVES = Left Ventricular Ejection Fraction; LVFS = Left Ventricular Fractional Shortening; WHO = World Health Organization