SLEEP, CIRCADIAN HORMONAL DYSREGULATION AND BREAST CANCER SURVIVAL

睡眠、昼夜荷尔蒙失调与乳腺癌生存

• 批准号: 7717933
• 负责人: David Spiegel
• 金额: $ 0.17万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717933
• 关键词: Address; Affective; Age; Aging; Anxiety; Anxiety Disorders; Breast Cancer Risk Factor; Cancer Etiology; Cancer Patient; Cessation of life; Circadian Rhythms; Computer Retrieval of Information on Scientific Projects Database; Corticotropin; Corticotropin-Releasing Hormone; Development; Disease; Disease Progression; Disruption; Elderly; Endocrine; Fatigue; Feeling; Functional disorder; Funding; Gene Expression; Grant; HPSE gene; Health; Homeostasis; Hormonal; Hormones; Human; Hydrocortisone; Immune; Immunologic Markers; Implant; Incidence; Institution; Lead; Life; Link; Long-Term Survivors; Longevity; Malignant Neoplasms; Measures; Mediating; Mediator of activation protein; Melatonin; Mental Depression; Metastatic Neoplasm to the Breast; Modeling; Mus; Natural Killer Cells; Obstructive Sleep Apnea; Outcome; Pain; Patient Self-Report; Patients; Pattern; Physiological; Play; Postmenopause; Process; Prognostic Factor; Psychosocial Factor; Quality of life; Recovery; Research; Research Personnel; Resistance; Resources; Restless Legs Syndrome; Risk; Role; Sleep; Sleep Disorders; Sleeplessness; Social support; Source; Spouses; Stimulus; Stress; Structure; Substance abuse problem; Symptoms; System; Time; United States National Institutes of Health; Woman; body-mind; circadian pacemaker; coping; day; depressive symptoms; experience; hypothalamic-pituitary-adrenal axis; immune function; improved; malignant breast neoplasm; mortality; outcome forecast; psychosocial; relating to nervous system; shift work; tumor growth

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We spend one-third of our lives asleep, yet little research has been done on the effects of sleep on resistance to cancer incidence and progression. There is a high incidence (63%) of self-reported sleep disruption in women with breast cancer and this has been shown to be associated with decreased longevity in these patients. While this association could be driven by more severe cancer causing an increase in sleep disruption, it is also possible that sleep disruption could lead to decreased survival time in these patients. It has been shown that women whose sleep is disrupted by nighttime shiftwork are at higher risk for breast cancer. Other types of sleep disruption common in post-menopausal women, such as obstructive sleep apnea, restless legs syndrome, and insomnia, could also have significant deleterious effects on longevity. Sleep is a critical time for energy conservation and neural homeostasis. The disruption of these processes could, very likely, lead to dysfunction of the nervous, endocrine, immune and other systems. Furthermore, disrupted sleep is often treatable, providing a potentially powerful means of improving both the quality of life and the prognosis of cancer patients. A growing body of evidence suggests that psychosocial factors have potentially powerful modulating effects on the course of cancer. Sleep may play a central role. There is growing scientific evidence and increasing public concern regarding the link between stress and health. One of the major consequences of stress is disruption of circadian rhythms, including the timing and structure of sleep and hormonal activity. Recent research indicates that such disruption predicts poor prognosis for breast cancer patients, and thus may be a mediating mind-body mechanism linking stress to disease progression. Disrupted sleep is important for its immediate consequences, such as fatigue, development of depressive and anxiety disorders, increased substance abuse, and reduced social support from spouses/partners as well as for its long-term consequences. Sleep is essential to human functioning and to disease recovery. Sleep problems are persistent among long-term survivors of breast cancer, and are associated with a poorer quality of life. Undisturbed sleep appears essential for coping with cancer and symptoms such as pain, because disturbed sleep causes decrements in the functioning of physiological systems critical to cancer defense, such as natural killer cell activity and lowers the threshold for experiencing negative stimuli and feelings. However, little is known about specific affective or psychosocial factors that may precede or influence disrupted sleep for women with breast cancer. There were 211,300 new cases of breast cancer in the US in 2003 and 39,800 deaths due to the disease. Breast cancer is largely a disease of aging, rare below the age of 50, and increasingly common with advancing age. Recent research provides evidence that disrupted circadian rhythms are associated with increased risk of breast cancer incidence and faster progression to mortality. We have observed that loss of normal diurnal cortisol rhythm, with peaks late in the day rather than, as normal, in the morning, predicts early mortality with breast cancer. This disrupted rhythm is associated with more awakenings during the night, with the increased awakenings, perhaps, even contributing to the sustained disruption of the cortisol rhythm. Recent studies have shown that nighttime shift work is associated with a higher risk of developing breast cancer. In a murine model, disrupting circadian cycles, including cortisol, produced a doubling of implanted tumor growth. There is evidence that abnormal circadian clock gene expression is associated with cancer. Thus, sleep disruption is a potentially modifiable mediating risk factor for breast cancer and its progression. We therefore propose to study sleep disruption as a prognostic factor in the progression of metastatic breast cancer, and its association with disrupted circadian patterns of cortisol, corticotropin releasing factor (CRF), ACTH, melatonin, and measures of immune function. The project has four Specific Aims with 6 Hypotheses. To address Aim 1, we will compare sleep and diurnal hormone patterns in 105 women with metastatic breast cancer to 25 age- and SES-matched healthy controls. For Aim 2, we will study the association between the sleep patterns of these 105 women with metastatic breast cancer and various psychosocial and physiological factors. For Aim 3, we will examine the sleep patterns of these 105 women with metastatic breast cancer and follow them throughout the progression of their disease to determine whether disrupted sleep predicts shorter survival. For Aim 4, we will conduct exploratory mediator analyses to investigate whether sleep disruption mediates the relation of psychosocial factors (such as depression, anxiety) to health outcomes (HPA axis measures, immune markers and ultimately survival).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们的生命的三分之一睡着了，但对睡眠对癌症发病率和进展的影响的研究很少。 乳腺癌女性的自我报告睡眠破坏的发病率很高（63％），这已被证明与这些患者的寿命降低有关。 尽管这种关联可能是由于更严重的癌症驱动的，导致睡眠中断增加，但睡眠中断也可能导致这些患者的生存时间降低。 已经表明，由于夜间班次的破坏睡眠的妇女患乳腺癌的风险较高。 绝经后妇女常见的其他类型的睡眠中断，例如阻塞性睡眠呼吸暂停，腿部不安综合征和失眠，也可能对寿命产生重大有害影响。 睡眠是节能和神经稳态的关键时刻。 这些过程的破坏很可能导致神经，内分泌，免疫和其他系统的功能障碍。 此外，通常可以治疗睡眠的破坏，提供了改善癌症患者生活质量和预后的潜在强大手段。 越来越多的证据表明，社会心理因素对癌症的进程具有强大的调节作用。 睡眠可能起着核心作用。 对压力与健康之间的联系越来越多的科学证据，并越来越关注。 压力的主要后果之一是昼夜节律的破坏，包括睡眠和荷尔蒙活动的时间和结构。 最近的研究表明，这种干扰预测了乳腺癌患者的预后不良，因此可能是将压力与疾病进展联系起来的介导的思维机制。 睡眠中断对于其直接后果很重要，例如疲劳，抑郁症和焦虑症的发展，增加药物滥用以及配偶/伴侣的社会支持以及其长期后果。睡眠对于人类功能和疾病康复至关重要。 睡眠问题在乳腺癌的长期幸存者中持续存在，并且与生活质量较差有关。 不受干扰的睡眠对于应对癌症和疼痛等症状似乎至关重要，因为睡眠障碍会导致对癌症防御至关重要的生理系统功能的降低，例如自然杀伤细胞活动，并降低了体验负面刺激和感觉的阈值。但是，对于可能在乳腺癌女性可能会发生或影响睡眠破坏的特定情感或社会心理因素的知之甚少。 2003年，美国有211,300例新的乳腺癌病例，由于该疾病而导致39,800例死亡。 乳腺癌在很大程度上是一种衰老的疾病，罕见的年龄低于50岁，并且随着年龄的增长而越来越普遍。最近的研究提供了证据表明，昼夜节律中断与乳腺癌发生率的风险增加和更快的死亡率有关。我们已经观察到，正常的昼夜皮质醇节奏的丧失，白天晚些时候的峰值，而不是正常的早晨，可以预测乳腺癌的早期死亡率。这种干扰的节奏与夜间更多的觉醒有关，觉醒的增加，甚至有助于持续破坏皮质醇节奏。最近的研究表明，夜间轮班工作与患乳腺癌的风险更高有关。在鼠模型中，破坏包括皮质醇在内的昼夜节律产生了植入肿瘤生长的一倍。有证据表明，异常的昼夜节律钟表基因表达与癌症有关。因此，睡眠破坏是乳腺癌及其进展的潜在可修改的介导危险因素。因此，我们建议将睡眠破坏作为转移性乳腺癌进展的预后因素，以及与皮质醇，皮质激素释放因子（CRF），ACTH，褪黑激素和免疫功能测量的昼夜昼夜昼夜的相关性。 该项目具有四个特定目标，并有6个假设。为了解决AIM 1，我们将比较105名转移性乳腺癌女性的睡眠和昼夜激素模式与25岁和SES匹配的健康对照。对于AIM 2，我们将研究这105位转移性乳腺癌女性的睡眠模式与各种社会心理和生理因素之间的关联。对于AIM 3，我们将检查这105名患有转移性乳腺癌的女性的睡眠模式，并在整个疾病的过程中跟随她们，以确定破坏的睡眠是否预测了较短的生存率。对于AIM 4，我们将进行探索性调解人分析，以调查睡眠破坏是否介导心理因素（例如抑郁症，焦虑）与健康结果的关系（HPA轴心测量，免疫标记和最终生存）。