Indicators of Accelerated Aging in Asian American Childhood Survivors

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Abstract With treatment advances for childhood cancer, over 80% of patients achieve long-term survival. To achieve cure, childhood cancer survivors (CCS) undergo intensive, multimodal treatment regimens including combinations of surgery, chemotherapy, radiation therapy, and hematopoietic stem cell transplantation. Such regimens put these patients at risk of adverse late health effects including cardiovascular disease, neurocognitive problems, endocrinopathies, mental health issues, and premature mortality. An important mechanism which may increase the risk of late effects in CCS is premature biological aging. A substantial percent of CCS experience frailty, a phenotype commonly studied in older adults which is characterized by reduction in at least three physical ability measurements. CCS also suffer from cancer-related neurocognitive impairment, which has been found in approximately 35% of CCS and includes declines in intelligence, attention, memory, processing speed, and executive function. Other markers of accelerated aging that have been identified in CCS include chronic inflammation and metabolic syndrome leading to abnormal body fat distribution, decreased proportion of lean body mass, and dyslipidemia symptoms. Missing from this research is the examination of markers of accelerated aging among racial and ethnic CCS groups other than non- Hispanic whites, as the majority of studies in this area have been limited to Caucasian populations. Studies set among older adults have shown variability in aging by race and ethnicity. Among East Asians, specific mitochondrial DNA variation has been identified that predisposes Asians to type 2 diabetes despite having lower mean body mass index than European populations. In comparative studies focused on CCS set in Asia, Asian CCS demonstrated worse treatment-related neurocognitive impairment compared to non-Hispanic whites and possess specific genetic susceptibilities for treatment-related toxicities such as neuropathy. Despite potential unique differences by race/ethnicity in accelerated aging in CCS, little research has been conducted in diverse populations. To address this research gap, we propose in this supplement to examine indicators of accelerated aging among Asian American CCS participating in a population-based R01 (1R01CA261888-01) compared to race- and age-matched controls. Our aims are: Aim 1: To assess cognitive performance in Asian American CCS compared to controls. Aim 2: To measure circulating biomarkers related to aging in Asian American CCS compared to controls. Aim 3: To assess changes in body-composition related to metabolic- aging in Asian American CCS compared to controls. The proposed research will provide important preliminary data to assess the potentially unique impacts of cancer-related treatment on accelerated aging among Asian American CCS. Such research may enable tailored surveillance and interventions to prevent late effects to which Asian American CCS may be uniquely susceptible.