Indicators of Accelerated Aging in Asian American Childhood Survivors

亚裔美国童年幸存者加速衰老的指标

• 批准号: 10910604
• 负责人: Joel E Milam
• 金额: $ 19.99万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10910604
• 关键词: Acceleration; Address; Adult; Affect; Age; Age Years; Aging; American; Area; Asia; Asian; Asian Americans; Asian population; Attention; Behavior; Biological Aging; Biological Markers; Body Composition; Body fat; Body mass index; Brain-Derived Neurotrophic Factor; California; Cardiovascular Diseases; Caucasians; Central Nervous System; Childhood; Childhood Cancer Survivor Study; Chronic; Cohort Studies; Combined Modality Therapy; Comparative Study; County; DNA Methylation; Data; Diagnosis; Dyslipidemias; East Asian; Elderly; Eligibility Determination; Ethnic Origin; European; Friends; Genetic Predisposition to Disease; Health; Hematopoietic Stem Cell Transplantation; Inflammation; Inflammatory; Intake; Intelligence; Interleukin-6; Intervention; Late Effects; Lead; Length; Life Style; Literature; Long-Term Effects; Los Angeles; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of brain; Measurement; Measures; Memory; Mental Health; Metabolic; Metabolic syndrome; Methotrexate; Mitochondrial DNA; Modality; Neurocognitive; Neurocognitive Deficit; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Nutritional; Operative Surgical Procedures; Oranges; Oxidative Stress; Parents; Participant; Patients; Phenotype; Physical activity; Plasma; Population; Population Heterogeneity; Population Study; Predisposition; Premature Mortality; Premature aging syndrome; Prevention; Race; Radiation therapy; Regimen; Research; Risk; SEER Program; Sampling; Siblings; Socioeconomic Status; Spouses; Survivors; Symptoms; Systemic disease; TNF gene; Telomere Shortening; Treatment Protocols; Treatment-Related Cancer; Treatment-related toxicity; Variant; cancer type; chemotherapy; childhood cancer survivor; circulating biomarkers; clinical biomarkers; cognitive function; cognitive performance; comparison control; cytokine; ethnic diversity; executive function; experience; frailty; high risk; insight; irradiation; lean body mass; muscle form; national surveillance; neoplasm registry; neurotoxic; population based; premature; prevent; processing speed; racial difference; racial diversity; recruit; telomere; tool; treatment effect

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.

抽象的 随着儿童癌症的治疗进展，超过80％的患者可实现长期生存。实现 治愈，儿童癌症幸存者（CCS）接受密集的多模式治疗方案 手术，化学疗法，放射治疗和造血干细胞移植的组合。这样的 方案使这些患者面临不良晚期健康影响的风险，包括心血管疾病， 神经认知问题，内分泌病，心理健康问题和过早死亡。一个重要的 可能会增加CCS后期作用风险的机制是生物学过早衰老。实质性 CCS的百分比体验脆弱，这是一种在老年人中通常研究的表型，其特征是 降低至少三个身体能力测量。 CC还患有与癌症相关的神经认知 损伤已在大约35％的CC中发现，包括智力下降， 注意，记忆，处理速度和执行功能。其他加速衰老的标记 在CC中发现的包括慢性炎症和代谢综合征，导致身体脂肪异常 分布，瘦体重的比例降低和血脂异常症状。这项研究缺失 是否检查了非非 - 除非非 - 西班牙裔白人，因为该领域的大多数研究都仅限于高加索人群。研究集 在老年人中，由于种族和种族的衰老变异性。在东亚人中，具体 线粒体DNA的变异已被鉴定出，尽管患有亚洲人，但易感亚洲人，尽管有2型糖尿病 平均体重指数低于欧洲人群。在比较研究中，集中于亚洲设定的CCS 与非西班牙裔相比 白色并具有针对治疗相关毒性（例如神经病）的特定遗传敏感性。尽管 种族/民族在CCS的加速衰老中的潜在独特差异，很少进行研究 在不同的人群中。为了解决这一研究差距，我们建议在此补充中研究 参加基于人群的R01（1R01CA261888-01）的亚裔美国人CC中加速衰老 与种族和年龄匹配的对照相比。我们的目标是：目标1：评估亚洲的认知表现 与对照组相比，美国CCS。目标2：测量与亚洲衰老有关的循环生物标志物 与对照组相比，美国CCS。目标3：评估与代谢相关的人体组成变化 与对照组相比，亚裔美国人CC的衰老。拟议的研究将提供重要的初步 数据以评估癌症相关治疗对亚洲加速衰老的潜在独特影响 美国CCS。这样的研究可能会实现量身定制的监视和干预措施，以防止晚期影响 亚裔美国人CC可能唯一容易受到影响。