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

Key Findings

Research conducted by St. Jude Children's Research Hospital has revealed significant insights into the genetic components associated with late-onset cardiomyopathy in survivors of childhood cancer. The study published in JAMA Network Open demonstrates that the genetic risk for developing this condition varies based on the age at which cancer treatment was initiated.

Study Overview

The relationship between genetic variants and late-onset cardiomyopathy risk has been underexplored in childhood cancer survivors. The study aimed to determine whether genetic patterns seen in the general population also apply to this specific group, particularly focusing on survivors who have been cancer-free for at least five years.

Research Insights

The investigation identified that common genetic variants in two specific genes, TTN and BAG3, were linked to a decreased risk of developing late-onset cardiomyopathy among childhood cancer survivors. Conversely, rare variants that elevate the risk for early-onset cardiomyopathy in the general population and among adult cancer survivors did not show a similar association in this cohort.

Understanding these genetic differences is crucial as survivors of childhood cancer face a 15-fold increased risk of cardiomyopathy compared to their healthy peers. This heightened vulnerability is attributed not only to cancer treatments but also to factors such as young age at diagnosis and other traditional risk elements related to heart disease. However, these aspects alone do not fully explain the elevated risk observed in these survivors.

Distinct Genetic Profiles

The research team, led by Dr. Yadav Sapkota from the Department of Epidemiology and Cancer Control at St. Jude, examined both common and rare genetic variants that contribute to late-onset cardiomyopathy in childhood cancer survivors. Their study involved 205 participants from the St. Jude Lifetime Cohort (SJLIFE) and 248 individuals from the Childhood Cancer Survivor Study (CCSS), focusing on those who developed cardiomyopathy related to cancer treatments.

Types of Cardiomyopathy

Dr. Sapkota noted that two main forms of dilated cardiomyopathy exist: familial early-onset, which typically runs in families and is associated with rare variants, and sporadic late-onset, which usually lacks a family history and is linked to common genetic variants. The current findings suggest that the genetic risk factors for late-onset cardiomyopathy among childhood survivors are distinct from those affecting early-onset forms.

Implications for Future Research

The findings underscore the necessity for tailored genetic screening processes that account for the differences in health outcomes between early- and late-onset cardiomyopathy. Enhanced understanding of these genetic variants could lead to improved risk assessment and management strategies for childhood cancer survivors.

Further Information

For more details, refer to the study titled TTN and BAG3 in Cancer Therapy-Related Cardiomyopathy Among Long-Term Survivors of Childhood Cancer, published in JAMA Network Open.