Epigenetics and Psychoneurologic Symptoms in Women with Breast Cancer

乳腺癌女性的表观遗传学和心理神经症状

• 批准号: 8152261
• 负责人: COLLEEN K JACKSON-COOK
• 金额: $ 64.74万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-29 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8152261
• 关键词: Address; Anxiety; Biological; Biological Assay; Biological Markers; Biological Process; Biometry; Breast Cancer Treatment; C-reactive protein; Cancer Etiology; Cancer Survivor; Chromatin; Chromosomal Instability; Chronic; Coupled; DNA Damage; DNA Repair; DNA Repair Gene; Development; Diagnosis; Disease; Distress; EZH2 gene; Early Diagnosis; Encapsulated; Epigenetic Process; Etiology; Event; Fatigue; Frequencies; Future; Gene Expression; Health; Histones; Impaired cognition; Individual; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-6; Intervention; Knowledge; Lead; Location; Longitudinal Studies; Malignant Neoplasms; Measures; Methylation; Molecular Cytogenetics; Neurocognitive; Outcome; Pain; Pattern; Polycomb; Process; Proteins; Quality of life; Reporting; Research; Research Personnel; Severities; Skin Cancer; Sleep disturbances; Staging; Survival Rate; Symptoms; Systemic Therapy; Telomere Shortening; Testing; Time; Tumor Necrosis Factor-alpha; Woman; Work; active method; base; biobehavior; cancer diagnosis; cancer therapy; chemotherapy; depressive symptoms; experience; genome-wide; high risk; improved; inflammatory pain; malignant breast neoplasm; meetings; oncology; prevent; response; survivorship; symptom management; telomere; treatment duration

Although advancements in breast cancer treatments have resulted in improved rates of survival, a majority of women with breast cancer (BC) experience distressing symptoms during treatment, which for some, persist into survivorship. The symptoms most frequently reported among women with BC include cognitive dysfunction (CD), depressive symptoms, anxiety, fatigue, sleep disturbances, and pain, which may be collectively called "psychoneurological (PN) symptoms." Inflammatory activation and epigenetic alterations have been associated with the etiology of cancer and with various chronic neurocognitive disorders. However, to date, no investigators have considered these epigenetic processes as possible mechanisms associated with the etiology of PN symptoms in women with BC. Given that epigenetic patterns have been shown to have plasticity, the further elucidation of the relationship of epigenetic alterations to the development and persistence of PN symptoms could provide foundational knowledge for the future development of predictive markers and treatments to address the epigenetic changes associated with PN symptoms in women with BC. Therefore, the specific aims of this study are to examine: 1. The frequency and severity of PN symptoms and the interrelationships among PN symptoms at each time point. 2. Levels of inflammation and to quantify the frequency and genome-wide localization of changes in epigenetic patterns across time following chemotherapy. 3. The relationships among inflammation, epigenetic changes, and the development, severity, and persistence of PN symptoms across time. To meet these aims, the proposed study will prospectively characterize PN symptoms (cognitive dysfunction; depressive symptoms and anxiety; fatigue; sleep disturbances; pain), inflammatory activation [(levels of C- reactive protein (CRP), tumor necrosis factor alpha (TNF-a), interleukin 1 beta (IL-1B), and interleukin 6 (IL- 6)], and epigenetic alterations in 75 women diagnosed with early-stage BC across 5 timepoints: prior to their receipt of chemotherapy, at the time of their fourth chemotherapy treatment, and at 6, 12, and 24 months following the initiation of chemotherapy. Epigenetic alterations will be detected by quantifying the: (1) frequency and genome-wide location of methylation; (2) expression of a histone methyltransferease, EZH2, which is a Polycomb group protein that is thought to be important for the early steps in the epigenetic "decision" process; and (3) telomere attrition, which can lead to alterations in chromatin compaction/gene expression. The study results may potentially deepen understanding regarding the biological processes underlying PN symptoms and lead to improved strategies for symptom management in women with BC.

尽管乳腺癌治疗的进步提高了生存率，但大多数患有乳腺癌的妇女在治疗期间会出现令人痛苦的症状，对一些人来说，这些症状会持续到生存期。在女性BC患者中最常见的症状包括认知功能障碍（CD）、抑郁症状、焦虑、疲劳、睡眠障碍和疼痛，这些症状统称为“神经心理症状”。炎症激活和表观遗传改变与癌症的病因学和各种慢性神经认知障碍有关。然而，到目前为止，还没有研究人员认为这些表观遗传过程可能与BC女性PN症状的病因学相关。鉴于表观遗传模式已被证明具有可塑性，进一步阐明表观遗传改变与PN症状的发展和持续之间的关系，可以为未来开发预测标记物和治疗方法提供基础知识，以解决与BC女性PN症状相关的表观遗传改变。