Genetic Factors In Treatment-Related Cardiovascular Complications In Survivors Of Childhood Acute Lymphoblastic Leukemia

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 ventricle 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 ventricle ejection fraction, and in NOD2 and ZNF267 genes in relation to fractional shortening. Conclusion: 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.