Indicators of Accelerated Aging in Asian American Childhood Survivors

摘要 随着儿童癌症治疗的进步，超过80%的患者实现了长期生存。实现 治愈，儿童癌症幸存者（CCS）接受强化，多模式治疗方案，包括 手术、化疗、放疗和造血干细胞移植的组合。等 治疗方案使这些患者处于不利的后期健康影响的风险中， 神经认知问题、内分泌疾病、心理健康问题和过早死亡。一个重要 可能增加CCS中迟发效应风险的机制是过早的生物老化。大幅 %的CCS经历虚弱，这是一种通常在老年人中研究的表型，其特征在于 至少有三项体能指标下降。CCS还患有癌症相关的神经认知障碍， 在大约35%的CCS中发现了损伤，包括智力下降， 注意力、记忆力、处理速度和执行功能。其他加速老化的标志， 包括慢性炎症和代谢综合征，导致身体脂肪异常 分布、瘦体重比例降低和血脂异常症状。在这项研究中缺失 是检查种族和民族CCS组中加速老化的标志物，而非 西班牙裔白人，因为该领域的大多数研究仅限于高加索人群。研究集 在老年人中，已经显示出种族和民族之间的衰老差异。在东亚人中， 线粒体DNA变异已被确定为使亚洲人易患2型糖尿病，尽管他们有 平均体重指数低于欧洲人群。在以亚洲CCS为重点的比较研究中， 与非西班牙裔相比，亚裔CCS显示出更差的治疗相关神经认知障碍 白人，并具有治疗相关毒性（如神经病变）的特定遗传易感性。尽管 CCS加速老化中人种/种族的潜在独特差异，很少进行研究 在不同的人群中。为了弥补这一研究空白，我们在本补编中建议审查 参与基于人群的R 01（1 R 01 CA 261888 -01）的亚裔美国CCS的加速老化 与种族和年龄匹配的对照组相比。我们的目标是：目标1：评估亚洲人的认知表现 美国CCS与对照组相比。目的2：测量亚洲人与衰老相关的循环生物标志物 美国CCS与对照组相比。目的3：评估与代谢相关的身体组成变化， 与对照组相比，亚裔美国人CCS的老化。这项研究将提供重要的初步 评估癌症相关治疗对亚洲人加速衰老的潜在独特影响的数据 美国CCS这种研究可以使有针对性的监测和干预措施，以防止后期影响， 亚裔美国人的CCS可能是唯一易感的。

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.