Scientists from St. Jude Children’s Research Hospital have uncovered distinct genetic factors influencing the risk of late-onset cardiomyopathy in childhood cancer survivors. Published in JAMA Network Open, the study shows that while common variants in TTN and BAG3 genes reduce cardiomyopathy risk—mirroring trends in the general population—rare variants linked to early-onset cases in adults do not apply to these survivors. The findings highlight the unique challenges faced by long-term childhood cancer survivors.
Childhood cancer survivors are 15 times more likely to develop cardiomyopathy than their healthy siblings, a risk exacerbated by cancer treatments, young age at diagnosis, and traditional heart disease factors. Yet, these elements alone don’t fully explain the heightened risk, prompting researchers to explore genetic contributors.
Led by Dr. Yadav Sapkota, the team analyzed data from 453 survivors across two cohorts, focusing on TTN (which produces the structural protein titin) and BAG3 (a regulatory protein). They discovered that common variants in these genes lowered the risk of late-onset cardiomyopathy, aligning with patterns seen in the general population. However, rare variants associated with early-onset cardiomyopathy in adults showed no effect in childhood survivors, underscoring the distinct genetic landscape of this group.
Dr. Sapkota explained, “In familial cases, rare variants often cause early-onset disease. But for late-onset cardiomyopathy in survivors, common variants with modest effects play a bigger role, similar to sporadic cases in the general population.”
The study emphasizes the need for tailored genetic screening to better assess cardiomyopathy risk in childhood cancer survivors. By recognizing the differences between early- and late-onset disease mechanisms, researchers aim to improve future risk prediction and personalized care for this vulnerable population.
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