How Cardiomyopathy Risk Varies by Age in Childhood Cancer Survivors?

Understanding how genetic factors influence late-onset cardiomyopathy in childhood cancer survivors has remained unclear, even though such links are well established in the general population. Researchers at St. Jude Children’s Research Hospital have taken a step toward filling this knowledge gap (1^✔ ✔Trusted Source
TTN and BAG3 in Cancer Therapy-Related Cardiomyopathy Among Long-Term Survivors of Childhood Cancer

Go to source). Their study examined whether genetic patterns associated with cardiomyopathy in the general public are also relevant to individuals who survived childhood cancer for at least five years.

The findings, published in JAMA Network Open, show that common genetic variants in the TTN and BAG3 genes are similarly linked to a reduced risk of late-onset cardiomyopathy in this group.

Unique Cardiomyopathy Risks in Childhood Cancer Survivors

Interestingly, rare genetic variants known to raise the risk of early-onset cardiomyopathy in both the general population and adult cancer survivors did not appear to influence the late-onset form of the disease in childhood cancer survivors. These results underscore the unique biological profile of childhood cancer survivors and the importance of tailored research in understanding their long-term health outcomes.

The increased cardiomyopathy risk is associated with certain cancer treatments and is further compounded by young age at diagnosis and traditional heart disease risk. However, these factors do not fully account for the increased level of risk childhood cancer survivors experience. Investigators are turning to genetics to help unravel survivors’ cardiomyopathy risk.

A team led by Yadav Sapkota, PhD, St. Jude Department of Epidemiology & Cancer Control, examined common and rare genetic variants associated with late-onset cardiomyopathy in the context of childhood cancer survivorship to shed light on these relationships. The researchers then compared these findings to other published studies, including those on dilated cardiomyopathy seen in the general public.

“There are two types of dilated cardiomyopathy,” Sapkota explains. “The first is familial, early-onset, meaning if your parents have it, then you are more likely to have it. These cases are usually associated with rare variants. The second is sporadic, late-onset, where there is generally no family history, but common variants have been identified in the general population.”

The researchers examined 205 survivors from the St. Jude Lifetime Cohort (SJLIFE) and 248 survivors from the Childhood Cancer Survivor Study (CCSS) with late-onset cancer treatment-related cardiomyopathy. They focused on genes where common and rare variants were shown to be highly enriched in patients with cardiomyopathy in the general population and survivors of adult cancer, primarily within TTN, the gene that encodes the structural protein titin, and BAG3, which encodes a multifunctional regulatory protein of the same name.

Genetic Factors in Childhood Cancer Survivors

This is also the case for sporadic and late-onset dilated cardiomyopathy in the general population. However, rare variants previously associated with increased risk of familial, early-onset dilated cardiomyopathy and early-onset cancer treatment–related cardiomyopathy in survivors of adult cancer showed no association, highlighting the unique genetic complexity of long-term childhood cancer survivorship.

“In familial diseases, rare variants with a high effect usually kick in when you are still young, contributing to early-onset forms of the condition. These observations can likely be implicated in early-onset cancer treatment–related cardiomyopathy, but not in our late-onset cancer treatment cardiomyopathy,” Sapkota said.

“Common variants usually confer a modest effect and contribute to late-onset forms of diseases. We had wondered if these variants associated with late-onset cancer treatment–related cardiomyopathy act similarly to the sporadic nature of dilated cardiomyopathy in the general population, which is, indeed, what we observe in this study.”

The study suggests that more accurate genetic variant screens driven by this better understanding and acknowledgment of the differences between early- and late-onset health outcomes may help improve risk assessment in the future.

Reference:

1. TTN and BAG3 in Cancer Therapy–Related Cardiomyopathy Among Long-Term Survivors of Childhood Cancer - (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2835512)

Source-Eurekalert