Understanding Ethnic Differences in Cancer: The Multiethnic Cohort Study

了解癌症的种族差异：多种族队列研究

• 批准号: 10716739
• 负责人: Christopher Alan Haiman
• 金额: $ 41.02万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10716739
• 关键词: Administrative Supplement; Adult; African; African American; African American population; Age; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Applications Grants; Archives; Asian Americans; Biological Aging; Biological Markers; Blood; Blood Vessels; California; Cause of Death; Cerebrospinal Fluid; Characteristics; Chronic Disease; Clinic; Clinical assessments; Cohort Analysis; Cohort Studies; Data; Data Linkages; Death Certificates; Dementia; Diagnosis; Diagnostic; Diet; Dietary Practices; Disease Outcome; Disparity; Education; Environmental Risk Factor; Epigenetic Process; Ethnic Origin; Ethnic Population; Evaluation; FDA approved; Foundations; Frequencies; Genetic; Genetic Predisposition to Disease; Grant; Hawaii; Household Air Pollution; Individual; Infrastructure; Investigation; Island; Japanese; Japanese American; Latino; Life Style; Light; Malignant Neoplasms; Manuscripts; Mediation; Medical Records; Medicare; Medicare claim; Metabolic; Metabolic Diseases; Modality; Modeling; Native Hawaiian; Neighborhoods; Nested Case-Control Study; Participant; Patients; Peer Review; Physical activity; Plasma; Population; Population Attributable Risks; Primary Care Physician; Private Practice; Prospective cohort; Race; Recording of previous events; Recurrence; Reporting; Research; Risk; Risk Adjustment; Risk Factors; Role; Sampling; Sleep; Socioeconomic Status; Specialist; Testing; Time; United States National Institutes of Health; Validation; Variant; Woman; Work; accurate diagnostics; apolipoprotein E-4; blood-based biomarker; burden of illness; clinical diagnosis; cohort; comparison control; cost; dementia risk; ethnic difference; ethnic disparity; ethnic minority; ethnic minority population; follow-up; genetic risk factor; genome wide methylation; human old age (65+); men; metabolomics; modifiable risk; mortality; multi-ethnic; neuroimaging; novel; polygenic risk score; population based; practice setting; prospective; racial disparity; racial minority; racial minority population; racial population; response; rural residence; sex; sex disparity; tau-1

PROJECT SUMMARY / ABSTRACT In Alzheimer's disease (AD) research to mitigate the disease burden, there is a critical need to better utilize prospective cohorts. The need is especially great for population-based cohorts that include significant numbers of racial/ethnic minority individuals. In light of this, we initiated AD and related dementias (ADRD) research in the Multiethnic Cohort Study (MEC; 1993-current), the largest and most diverse cancer cohort in the US, composed at baseline of >215,000 adults of five ancestries (African, Japanese, Latino, Native Hawaiian, White) sampled in Hawaii and Southern California. We observed that the AD rates and the known risk factor associations in the MEC-Medicare linkage data are highly comparable to those reported in clinic-based studies, which assures the quality and generalizability of the MEC data for AD/ADRD research. We also found substantially higher AD risks and APOE e4 frequencies among Native Hawaiians as well as African Americans, compared to Whites. This and other important findings speak to the unique values of the MEC for AD/ADRD disparities research. However, one recurrent concern is that the AD/ADRD definitions in MEC are solely based on Medicare claims and, thus, may include misclassifications. Medicare claims-based disease outcomes are validated against clinical diagnosis. This approach is, however, less reliable for AD/ADRD because the current diagnostic gold standard, neuroimaging or cerebrospinal fluid biomarkers, is often inaccessible or intolerable, particularly to individuals of racial/ethnic minorities, rural residences and older ages, while clinical assessment without these biomarkers has known low accuracy. In this context, the blood-based maker (BBM) newly approved by FDA for initial screening of AD, phosphorylated tau-181 (pTau-181), provides a vital opportunity to robustly validate AD cases in MEC, while at the same time producing timely evaluation of the BBM by race/ethnicity. Thus, we propose to (Aim 1) replicate the association between plasma pTau-181 and ~570 incident AD cases using archived blood collected within 5 years of the first Medicare claim in a nested case- control study. We will evaluate the association overall and by sex, race/ethnicity and APOE e4. We will also (Aim 2) identify the determinants of plasma pTau-181 in AD cases, among the case-related, demographic (sex, race/ethnicity, age cohort, education, neighborhood socioeconomic status), genetic (APOE, polygenic risk score) and modifiable risk factor (vascular-metabolic disease history, physical activity, diet quality, sleep duration) characteristics available from the long-term, prospective follow-up, in order to understand the biomarker variation. The proposed work is within the scope of the active MEC grant (U01 CA164973; 2022-2027), as it will enhance the cohort infrastructure for investigations of genetic, lifestyle and environmental risk factors for an important chronic disease in US adults across multiple racial/ethnic groups. Given the breadth and depth of the cancer and other chronic disease research that has been supported by the MEC, this proposed BBM-based validation and investigation of AD is likely to stimulate an array of additional activities leading to progress on AD/ADRD research.

项目概要/摘要 在减轻疾病负担的阿尔茨海默病 (AD) 研究中，迫切需要更好地利用 前瞻性队列。对于包含大量人员的基于人群的群体来说，这种需求尤其巨大 少数种族/族裔个体。鉴于此，我们在 多种族队列研究（MEC；1993 年至今），美国最大且最多样化的癌症队列， 基线由超过 215,000 名具有五个血统的成年人组成（非洲人、日本人、拉丁裔、夏威夷原住民、白人） 采样于夏威夷和南加州。我们观察到 AD 率和已知的风险因素 MEC-医疗保险链接数据中的关联与临床研究中报告的关联高度相似， 这确保了 AD/ADRD 研究的 MEC 数据的质量和普遍性。我们还发现 夏威夷原住民和非裔美国人的 AD 风险和 APOE e4 频率显着升高， 与白人相比。这一重要发现说明了 MEC 对于 AD/ADRD 的独特价值 差异研究。然而，一个反复出现的问题是 MEC 中的 AD/ADRD 定义仅基于 医疗保险索赔，因此可能包括错误分类。基于医疗保险索赔的疾病结果是 根据临床诊断进行验证。然而，这种方法对于 AD/ADRD 来说不太可靠，因为当前的 诊断金标准，神经影像学或脑脊液生物标志物，通常难以获得或无法忍受， 特别是针对少数种族/族裔、农村居民和老年人，同时进行临床评估 如果没有这些生物标志物，准确性就会很低。在此背景下，基于血液的制造商（BBM）新 FDA 批准磷酸化 tau-181 (pTau-181) 用于 AD 初步筛查，为 强有力地验证 MEC 中的 AD 案例，同时通过以下方式及时对 BBM 进行评估 种族/民族。因此，我们建议（目标 1）复制血浆 pTau-181 和 ~570 之间的关联 使用在嵌套病例中首次医疗保险索赔后 5 年内采集的存档血液的 AD 事件病例 - 对照研究。我们将按性别、种族/民族和 APOE e4 对关联进行整体评估。我们还将（目标 2) 确定 AD 病例中血浆 pTau-181 的决定因素，其中包括病例相关的人口统计因素（性别、 种族/族裔、年龄组、教育程度、社区社会经济地位）、遗传（APOE、多基因风险评分） 和可改变的危险因素（血管代谢疾病史、体力活动、饮食质量、睡眠时间） 从长期、前瞻性随访中获得的特征，以便了解生物标志物的变化。 拟议的工作属于 MEC 现行拨款（U01 CA164973；2022-2027）的范围，因为它将增强 用于调查遗传、生活方式和环境风险因素的队列基础设施 美国多个种族/族裔群体的成年人患有慢性疾病。鉴于癌症的广度和深度， MEC 支持的其他慢性病研究，提出了基于 BBM 的验证和 对 AD 的调查可能会刺激一系列额外的活动，从而推动 AD/ADRD 研究取得进展。