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。要实现 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、放射治疗和造血干细胞移植的组合。是这样的 这些方案将这些患者置于包括心血管疾病在内的不利的晚期健康影响的风险中， 神经认知问题、内分泌疾病、精神健康问题和过早死亡。一个重要的 可能增加CCS后遗症风险的机制是过早的生物衰老。一大笔钱 有百分比的CCS经历脆弱，这是老年人普遍研究的一种表型，其特征是 至少减少了三项体能测量。CCS还患有癌症相关的神经认知 损害，已在大约35%的CC中发现，包括智力下降， 注意力、记忆力、处理速度和执行功能。其他加速衰老的标志 在CCS中被发现包括慢性炎症和导致异常体脂的代谢综合征 分布、瘦体重比例下降，以及血脂异常症状。在这项研究中缺失 是不是在种族和民族CCS群体中检查加速老化的标志 西班牙裔白人，因为这一领域的大多数研究仅限于高加索人群。研究套装 在老年人中，不同种族和族裔的人在老龄化方面表现出差异。在东亚人中，特定的 线粒体DNA变异已被确定为易患2型糖尿病的亚洲人，尽管 平均体重指数低于欧洲人口。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患者表现出更严重的治疗相关神经认知障碍 白人和对与治疗相关的毒性，如神经病，具有特定的遗传易感性。尽管 在CCS中，种族/民族在加速衰老中的潜在独特差异，很少有研究进行 在不同的人群中。为了解决这一研究差距，我们在本补编中建议审查以下指标 参与基于人群的R01的亚裔美国人CCS中的加速老龄化(1R01CA261888-01) 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与对照的比较。目的2：测量亚洲人群中与衰老相关的循环生物标志物 美国CCS与对照的比较。目标3：评估与代谢相关的身体成分的变化 与对照组相比，亚裔美国人CCS的衰老。拟议的研究将提供重要的初步 评估癌症相关治疗对亚洲人加速老龄化的潜在独特影响的数据 美国CCS。这种研究可能会使量身定做的监测和干预措施成为可能，以防止对 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.