Cardio-oncology & otherCase-control study
Gene-Level Analysis of Anthracycline-Induced Cardiomyopathy in Cancer Survivors
- Genetic association study (whole-exome sequencing, matched case-control discovery with independent replication)
- logic regression (machine learning)
- 3 independent replication cohorts
Authors' conclusion
In our study, SNP sets having 1 or no copies of P2RX7 variant alleles were associated with reduced risk of cardiomyopathy, presenting a potential therapeutic target to mitigate cardiac outcomes in cancer survivors.
Study context
- Population
- Childhood cancer survivors exposed to anthracyclines (COG study ALTE03N1); replication in COG, BMTSS and CCSS cohortsdiscovery cohort
- Participants
- 278 survivors
- Comparison
- Gene-level SNP combinations vs anthracycline-induced cardiomyopathy
- Casesn = 129
- Controln = 149reference
- Outcome
- Gene-level associations with cardiomyopathy (significance threshold 6.93 × 10-6)
Main finding
As reported in the abstract
Gene-level association with cardiomyopathy (P2RX7)
P2RX7 vs ControlEstimate (95% CI)P value
discovery (COG ALTE03N1)
OR 0.10(0.04–0.27)
P = 2.19 × 10-6replication (CCSS cohort)
HR 0.65(0.47–0.90)
P = 0.009Observational data: associations, not effects.
Further findings
SNP-level replication of discovery genes
- Individual single nucleotide polymorphisms (SNPs) across all discovery genes, except FBN3, replicated
Original publication
Gene-Level Analysis of Anthracycline-Induced Cardiomyopathy in Cancer Survivors. JACC CardioOncol. Published 14 September 2023. doi:10.1016/j.jaccao.2023.06.007
Summarised from the published abstract; every number is checked against it