Sleep and Cancer: Evaluation of Risk and Insights into Mechanisms

睡眠与癌症：风险评估和机制洞察

• 批准号: 9900573
• 负责人: Peggy Reynolds
• 金额: $ 51.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-04 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900573
• 关键词: Address; Adult; Affect; Area; Biological Assay; Biological Markers; Biological Rhythm; Blood specimen; Breast; California; Cancer Burden; Cancer Control; Carcinogens; Cardiovascular Diseases; Cell Aging; Centers for Disease Control and Prevention (U.S.); Characteristics; Chronic; Circadian Dysregulation; Cohort Studies; Colorectal; Country; Data; Data Reporting; Development; Diabetes Mellitus; Dimensions; Disease; Endometrial; Epidemic; Epidemiology; Equilibrium; Etiology; Evaluation; Health; Hour; Human; Immune Sera; Immunologic Markers; Individual Differences; Inflammation; Inflammatory Response; Intervention; Lead; Length; Linear Models; Link; Literature; Logistic Regressions; Maintenance; Malignant Neoplasms; Measures; Mission; Modeling; Non-Hodgkin' s Lymphoma; Obesity; Outcome; Participant; Pathway interactions; Patient Self-Report; Periodicity; Personal Satisfaction; Persons; Physiological; Physiological Processes; Play; Prevalence; Prevention; Process; Production; Public Health; Research; Research Priority; Research Project Grants; Resources; Risk; Risk Estimate; Risk Factors; Role; Running; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Thyroid Gland; Uncertainty; United States National Institutes of Health; Wakefulness; Woman; anti-cancer; cancer diagnosis; cancer prevention; cancer risk; cancer site; carcinogenesis; circadian; circulating biomarkers; cohort; cytokine; design; epidemiology study; hazard; insight; interest; malignant breast neoplasm; melanoma; modifiable risk; mortality; neoplasm registry; preference; prospective; response; sleep health; sleep quality; teacher; telomere

Project Summary/Abstract The CDC recently declared insufficient sleep to be a “public health epidemic,” noting that an estimated 50-70 million US adults have sleep or wakefulness disorders. Although it is well-recognized that insufficient sleep increases the risk for many chronic conditions, the role of sleep in the development of cancer is unclear. While epidemiologic studies are sparse, they have yielded some provocative but inconsistent findings. Such inconsistencies may reflect the complexity of underlying etiologic mechanisms. Sleep plays a fundamental role in the maintenance of a number of key processes integral to carcinogenesis, including inflammation and cellular replication and proliferation. Furthermore, there may be individual differences in vulnerability to the effects of sleep deficiency, depending on chronotype (i.e., whether one’s endogenous biological rhythm of sleep/wakefulness follows a morning or evening preference). Our objective is to advance the understanding of how sleep deficiency may influence cancer risk, considering both potential underlying mechanisms and host vulnerability. The study will capitalize on resources available from the California Teachers Study (CTS) in which 65,000 women have provided detailed self-reported data on sleep and chronotype, a subset of whom have also provided blood samples available for the conduct of biomarker assays to quantify physiologic effects. The specific aims are to: 1.) evaluate cancer risks associated with self-reported sleep deficiency among CTS participants; 2.) assess the relationship between self-reported sleep deficiency and biomarkers of physiologic effect for chronic inflammation and telomere length; 3.) evaluate the degree to which cancer risks and the physiologic responses to sleep deficiency vary by chronotype. In addressing each of these aims, several specific dimensions of sleep deficiency will be considered, including poor sleep quality, extremes in sleep duration, fragmented sleep and long sleep latency. Cases of invasive breast and other selected commonly-diagnosed cancers (colorectal, melanoma, endometrial, non-Hodgkin’s lymphoma, thyroid) will be identified via linkage to the California Cancer Registry. Biomarker assays will be run on 800 blood samples collected from non- cancer cases within a year of the sleep and chronotype data. Multiplexed immunometric assays will be used to quantify levels of circulating biomarkers of inflammation. Quantitative PCR will be used to measure telomere length. Cox Proportional Hazards and Ordinary Logistic Regression models will be used to estimate risks for each dimension of sleep deficiency, adjusting for other known risk factors. Multivariable linear models will be used to characterize the relationship between the biomarkers and specific dimensions of sleep. Initial models will be expanded, incorporating chronotype to explore potential differences in risk and/or effect by chronotype. The long-term objective of this project supports the NCI’s mission to reduce the burden of cancer by furthering our understanding of its etiology and avenues for prevention. Additionally, it supports NIH’s recently identified priority to advance the understanding of sleep and circadian functions in health and disease.

项目概要/摘要 疾病预防控制中心 (CDC) 最近宣布睡眠不足是一种“公共卫生流行病”，并指出估计有 50-70 数以百万计的美国成年人患有睡眠或觉醒障碍，尽管众所周知，睡眠不足。 睡眠会增加许多慢性病的风险，但睡眠在癌症发展中的作用尚不清楚。 流行病学研究很少，但得出了一些具有争议性但不一致的发现。 不一致可能反映了潜在病因机制的复杂性，睡眠起着重要作用。 维持致癌作用所必需的许多关键过程，包括炎症和 此外，细胞复制和增殖的脆弱性可能存在个体差异。 睡眠不足的影响，取决于生物钟类型（即一个人的内源性生物节律是否 睡眠/清醒遵循早晨或晚上的偏好）。 考虑到潜在的潜在机制和宿主，睡眠不足如何影响癌症风险 该研究将利用加州教师研究 (CTS) 提供的资源。 其中 65,000 名女性提供了有关睡眠和睡眠时间类型的详细自我报告数据，其中一部分 还提供了可用于进行生物标志物测定以量化生理效应的血液样本。 具体目标是： 1.) 评估 CTS 中与自我报告的睡眠不足相关的癌症风险 2.) 评估参与者自我报告的睡眠不足与生理生物标志物之间的关系 对慢性炎症和端粒长度的影响；3.) 评估癌症风险的程度和 对睡眠不足的生理反应因时间类型而异。在实现这些目标时，有几个具体的目标。 将考虑睡眠不足的维度，包括睡眠质量差、睡眠时间极端、 睡眠碎片化和睡眠潜伏期长等常见的侵入性乳腺病例。 癌症（结直肠癌、黑色素瘤、子宫内膜癌、非霍奇金淋巴瘤、甲状腺癌）将通过链接进行识别 加州癌症登记处的生物标志物检测将对从非非癌症患者收集的 800 份血液样本进行。 一年内的癌症病例的睡眠和时间型数据将用于进行多重免疫测定。 定量PCR将用于测量端粒 Cox 比例风险和普通 Logistic 回归模型将用于风险估计。 睡眠不足的每个维度，都会调整其他已知的风险因素。 用于表征生物标志物与睡眠特定维度之间的关系。 将进行扩展，纳入时间类型以探索不同时间类型的风险和/或影响的潜在差异。 该项目的长期目标支持 NCI 的使命，即通过进一步促进减少癌症负担 此外，它支持 NIH 最近确定的方法。 优先推进对健康和疾病中睡眠和昼夜节律功能的了解。