Biobehavioral pathways linking stress and cancer progression

连接压力和癌症进展的生物行为途径

• 批准号: 8550036
• 负责人: JENNIFER L. STEEL
• 金额: $ 41.78万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8550036
• 关键词: Adopted; Adoption; Adverse event; Age of Onset; Alcohol consumption; Arousal; Behavior; Behavioral; Biological Markers; Buffers; Carcinoma; Cessation of life; Chronic stress; Cirrhosis; Demographic Aging; Demographic Factors; Development; Diagnosis; Diet; Disease; Disease Progression; Emotions; Ethnic Origin; Event; Exposure to; Fatty acid glycerol esters; Gender; Goals; Growth and Development function; HMGB1 Protein; HMGB1 gene; Health; Health behavior; Hepatic; Hepatobiliary; Individual; Inflammation; Inflammatory; Intervention; Lead; Life; Life Cycle Stages; Life Experience; Link; Malignant Neoplasms; Mediating; Mediator of activation protein; Metastatic Neoplasm to the Liver; Modeling; Morbidity - disease rate; Neoplasm Metastasis; Neuraxis; Neurobiology; Pathway interactions; Patients; Physiological; Physiological Processes; Population; Process; Prospective Studies; Psychosocial Stress; Quality of life; Readiness; Recording of previous events; Recurrence; Reporting; Research; Resources; Risk; Risk Factors; Social support; Staging; Stress; Time; Tobacco use; United States; behavior change; biobehavior; biological adaptation to stress; body-mind; cancer diagnosis; cancer type; coping; cytokine; early onset; effective intervention; experience; hypothalamic-pituitary-adrenal axis; illness perceptions; improved; loved ones; low socioeconomic status; meetings; mortality; novel; optimism; psychobiologic; psychologic; resilience; sex; social; stressor; tumor growth; tumor microenvironment; tumor progression

DESCRIPTION (provided by applicant): In 2010, over 11.5 million people were living with cancer in the United States and over 500,000 new cases are expected to be diagnosed each year. The life threatening and unpredictable course of cancer makes it a particularly stressful lif experience. Stress may be defined as when the demands being placed on an individual are perceived as threatening or harmful and exceed the resources available to manage the stressor. Decades of research have shown that stress is associated with maladaptive health behaviors (e.g., high fat diet) as well as increased risk of morbidity and mortality. The goal of this prospective study is to examine the mechanistic pathways linking chronic stress and engagement in maladaptive health behaviors with disease progression in people diagnosed with hepatobiliary carcinoma. The proposed study will begin to elucidate the biobehavioral pathways linking stress and health behaviors with disease progression in the context of cancer. The aims and hypotheses of this study are: (1) to investigate predictors of the psychological and physiological stress response to a diagnosis or recurrence of hepatobilary carcinoma. We expect that people who report a past history of early adverse events (e.g., death of a loved one, abuse) will report higher levels of perceived stress and elevations in biomarkers of inflammation. Early adverse events are expected to be associated with an earlier age of onset of these maladaptive health behaviors (e.g., alcohol use) and contributed to the risk factors associated with the development of cancer (e.g., cirrhosis); (2) to examine the dynamic link between stress and health behaviors over time in people diagnosed with hepatobiliary carcinoma. We expect high levels of chronic stress to be associated with (a) attempts to change maladaptive health behaviors or adopt adaptive health behaviors, or (b) attempts to decrease physiological arousal by continued use or re-initiation of maladaptive health behaviors. We expect that a positive illness perception will mediate the link between perceived stress and health behaviors and that problem focused coping and social support will moderate this relationship. Engaging in maladaptive behaviors to reduce stress will be mediated by negative illness perceptions and moderated by emotion focused coping and lack of social support; (3) to explore the links between stress, health behaviors, and biomarkers of inflammation on disease progression. We expect that patients with a combination of chronic stress and/or engagement in maladaptive health behaviors will have abnormal levels of biomarkers of inflammation and more rapid tumor growth and development of intra- and extra-hepatic metastases when compared to patients with lower levels of perceived stress or adaptive health behaviors. The proposed study is responsive to the RFA which request studies that will "examine mediating and moderating factors such as individual demographic (age, gender/sex, ethnicity) and psychological (vulnerabilities, resilience) differences, risk factors, early exposure to stress". The findings of this study are expected to lead to potential psychological and behavioral targets for interventions to improve quality of life and reduce mortality in people diagnosed with cancer.

描述（由申请人提供）：2010年，美国有超过1150万人患有癌症，预计每年将诊断出超过50万例新病例。癌症的生命威胁和不可预测的过程使其成为一个特别紧张的生活经历。压力可以被定义为当对个人的要求被认为是威胁或有害的，并超过可用的资源来管理压力。几十年的研究表明，压力与适应不良的健康行为有关（例如，高脂肪饮食）以及发病率和死亡率风险增加。这项前瞻性研究的目的是检查慢性压力和参与适应不良的健康行为与诊断为肝胆癌的人的疾病进展之间的机制途径。拟议的研究将开始阐明在癌症背景下将压力和健康行为与疾病进展联系起来的生物行为途径。本研究的目的和假设是：（1）探讨肝胆癌诊断或复发后心理和生理应激反应的预测因素。我们希望报告早期不良事件既往史的人（例如，亲人死亡、虐待）将报告更高水平的感知压力和炎症生物标志物的升高。早期不良事件预计与这些适应不良健康行为的发病年龄较早相关（例如，酒精使用）并促成与癌症发展相关的风险因素（例如，肝硬化）;（2）检查压力和健康行为之间的动态联系，随着时间的推移，在人们诊断为肝胆癌。我们认为高水平的慢性压力与以下因素有关：（a）试图改变适应不良的健康行为或采取适应性健康行为，或（B）试图通过持续使用或重新开始适应不良的健康行为来降低生理唤醒。我们预期，积极的疾病感知将介导感知压力和健康行为之间的联系，而以问题为中心的应对和社会支持将缓和这种关系。参与适应不良行为以减轻压力将通过负面疾病感知来介导，并通过情绪集中应对和缺乏社会支持来调节;（3）探索压力，健康行为和炎症生物标志物对疾病进展的关系。我们预计，与具有较低水平的感知压力或适应性健康行为的患者相比，具有慢性压力和/或参与适应性不良健康行为的患者将具有异常水平的炎症生物标志物和更快的肿瘤生长以及肝内和肝外转移的发展。拟议的研究是对RFA的回应，RFA要求研究“审查中介和调节因素，如个人人口统计（年龄，性别/性别，种族）和心理（脆弱性，复原力）差异，风险因素，早期暴露于压力”。这项研究的结果有望为干预措施提供潜在的心理和行为目标，以改善癌症患者的生活质量并降低死亡率。