Genetic Factors Influencing Cardiomyopathy Risk in Childhood Cancer Survivors Vary by Age of Onset

New research has shed light on the complex relationship between genetics and the risk of developing cardiomyopathy among survivors of childhood cancer. Published in JAMA Network Open, the study conducted by scientists at St. Jude Children's Research Hospital investigated how specific genetic variants, both common and rare, influence the likelihood of late-onset cardiomyopathy—a type of heart muscle disease that can emerge years after cancer treatment.

Despite the high risk of cardiomyopathy in childhood cancer survivors—who are about 15 times more likely to develop this condition than their healthy siblings—the genetic factors that predispose them to late-onset forms of the disease have remained poorly understood. The research focused on variants in the genes TTN, which encodes structural protein titin, and BAG3, which encodes a multifunctional regulatory protein. Findings revealed that common variants in these genes are associated with a decreased risk of late-onset cardiomyopathy in childhood cancer survivors, similar to patterns observed in the general population with dilated cardiomyopathy.

Interestingly, rare variants that are linked to early-onset, familial dilated cardiomyopathy in the general population—often carrying a high genetic effect—were not associated with late-onset cardiomyopathy in childhood cancer survivors. This distinction underscores the different genetic mechanisms involved in early versus late-onset disease and highlights the unique burden faced by this group.

"In familial diseases, rare high-impact variants usually lead to early disease onset, but in late-onset cases, common variants with modest effects seem to play a greater role," explained lead researcher Dr. Yadav Sapkota. "Our study suggests that genetic screening tailored to these differences could improve risk assessment and management for survivors."

The study analyzed data from over 200 childhood cancer survivors and compared their genetic profiles with existing data. The results emphasize that childhood cancer survivorship involves distinct genetic influences that differ from those in adult survivors and the general population, stressing the importance of personalized approaches to long-term care."