Abstract
Aim: Cardiovascular disease represents one of the main causes of secondary morbidity and mortality in patients with childhood cancer. Patients & methods: To further address this issue, we analyzed cardiovascular complications in relation to common and rare genetic variants derived through whole-exome sequencing from childhood acute lymphoblastic leukemia survivors (PETALE cohort). Results: Significant associations were detected among common variants in the TTN gene, left ventricular ejection fraction (p ≤ 0.0005), and fractional shortening (p ≤ 0.001). Rare variants enrichment in the NOS1, ABCG2 and NOD2 was observed in relation to left ventricular ejection fraction, and in NOD2 and ZNF267 genes in relation to fractional shortening. Following stratification according to risk groups, the modulatory effect of rare variants was additionally found in the CBR1, ABCC5 and AKR1C3 genes. None of the associations was replicated in St-Jude Lifetime Cohort Study. Conclusion: Further studies are needed to confirm whether the described genetic markers may be useful in identifying patients at increased risk of these complications.