Role of disparities and aging biomarkers in accelerated cardiac aging among adolescent and young adult cancer survivors

PROJECT SUMMARY AND ABSTRACT Cancer in adolescents and young adults (AYA) is defined as a diagnosis in individuals aged 15-39-years and is diagnosed in approximately 90,000 AYAs each year. Current treatment regimens for AYAs diagnosed with cancer often include cardiotoxic treatment regimens, which have been associated with increased risk of

cardiovascular dysfunction in survivors. Our preliminary data indicates that hearts in AYA cancer patients exposed to cardiotoxic treatment modalities have a functional phenotype that appears to mirror heart function in non-treatment exposed patients who are decades older. The incidence of this possible accelerated cardiac

aging phenotype in the survivor AYA cancer population is unknown, potential differences by race/ethnicity and genetic ancestry are unclear, and how known biological markers of aging correlate with heart function and potentially further influence the development of cardiotoxicity has not been investigated. To address this gap in

our understanding of cardiac aging in survivors of AYA cancer, we will test the overall hypothesis that an accelerated cardiac aging phenotype contributes to the development of poor cardiovascular health in survivors of AYA cancer, and that other markers of aging can further identify those at greatest risk for cardiovascular

disfunction. Towards this, the proposal has two objectives: 1) to elucidate and define accelerated cardiac aging in a diverse survivors of AYA cancer population (N=1,200) and 2) to identify predictors of an accelerated cardiac aging phenotype and the impact of race/ethnicity, genetic ancestry, social determinants of health, and

established aging biomarkers on this phenotype. To achieve these objectives, this proposal will leverage a diverse survivors of AYA cancer cohort anchored to echocardiographic assessments of cardiac function: Project DANCES. Data and biospecimens will enable investigation into accelerated cardiac aging and multi-

level assessment (individual, neighborhood, and population) of drivers of this phenotype. Established aging biomarkers will also be analyzed to identify relationships with accelerated cardiac aging. With the overall 5- year survival rate for AYA cancer patients remaining over 84%, there is a growing segment of survivors of AYA

cancer who have the potential to enjoy several more decades of life, cancer-free, highlighting the importance of prioritizing their long-term health post-cancer treatment. Cardiac dysfunction and morbidity is a major late effect in this population and the proposed research efforts are designed to identify risk factors and drivers of

these events – across a diverse AYA patient population.