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

基本信息

批准号：
8711107
负责人：
COLLEEN K JACKSON-COOK
金额：
$ 58.02万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-29 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8711107
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

项目摘要

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导致生存率提高，但大多数乳腺癌妇女（BC）在治疗过程中经历了令人痛苦的症状，对于某些人来说，这一直持续存在生存。 BC女性中最常出现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，这些症状可以集体称为“心理外科学（PN）症状”。炎症激活和表观遗传改变与癌症的病因和各种慢性神经认知疾病有关。但是，迄今为止，尚无研究人员认为这些表观遗传过程是与BC女性PN症状病因相关的可能机制。鉴于表观遗传模式已被证明具有可塑性，因此进一步阐明了表观遗传改变与PN症状的发展和持久性的关系，可以为未来的预测标志物和治疗的发展提供基本知识，以解决与BC女性与PN症状相关的表观遗传变化。因此，本研究的具体目的是检查： 1。PN症状的频率和严重程度以及每个时间点PN症状之间的相互关系。 2。炎症水平，并量化化疗后，整个时间的表观遗传模式变化的频率和全基因组定位。 3。炎症，表观遗传变化以及PN症状的发展，严重程度和持久性之间的关系。 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在5个时间点上诊断为BC早期的75名妇女在接受化学疗法之前，在接受化学疗法的6、12和24个月之前，会发生量化甲基化的甲基化甲基甲酸盐（2），将其属于：（1）蛋白质对表观遗传学“决策”过程的早期步骤很重要；

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The relationship of cognitive performance to concurrent symptoms, cancer- and cancer-treatment-related variables in women with early-stage breast cancer: a 2-year longitudinal study.

DOI：
10.1007/s00432-016-2163-y
发表时间：
2016-07
期刊：
Journal of cancer research and clinical oncology
影响因子：
3.6
作者：
Lyon DE;Cohen R;Chen H;Kelly DL;Starkweather A;Ahn HC;Jackson-Cook CK
通讯作者：
Jackson-Cook CK

Relationship of systemic cytokine concentrations to cognitive function over two years in women with early stage breast cancer.

DOI：
10.1016/j.jneuroim.2016.11.002
发表时间：
2016-12-15
期刊：
JOURNAL OF NEUROIMMUNOLOGY
影响因子：
3.3
作者：
Lyon, Debra E.;Cohen, Ronald;Chen, Huaihou;Kelly, Debra L.;McCain, Nancy L.;Starkweather, Angela;Ahn, Hyochol;Sturgill, Jamie;Jackson-Cook, Colleen K.
通讯作者：
Jackson-Cook, Colleen K.

Longitudinal Analysis of Sleep Disturbance in Breast Cancer Survivors.

DOI：
10.1097/nnr.0000000000000578
发表时间：
2022-05-01
期刊：
NURSING RESEARCH
影响因子：
2.5
作者：
Yang, Gee Su;Starkweather, Angela R.;Lynch Kelly, Debra;Meegan, Taylor;Byon, Ha Do;Lyon, Debra E.
通讯作者：
Lyon, Debra E.

Perceived Stress Levels, Chemotherapy, Radiation Treatment and Tumor Characteristics Are Associated with a Persistent Increased Frequency of Somatic Chromosomal Instability in Women Diagnosed with Breast Cancer: A One Year Longitudinal Study.