Biobehavioral pathways linking stress and cancer progression

描述（由申请人提供）：2010年，美国有超过1150万人患有癌症，预计每年将有超过50万的新病例被诊断出来。癌症威胁生命和不可预测的过程使它成为一种特别紧张的生活经历。压力可以定义为当施加在个人身上的要求被认为是威胁或有害的，并且超出了管理压力源的可用资源。几十年的研究表明，压力与适应不良的健康行为（如高脂肪饮食）以及发病率和死亡率的增加有关。本前瞻性研究的目的是探讨慢性应激和参与适应不良健康行为与肝癌患者疾病进展之间的机制途径。这项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)探讨对肝癌诊断或复发的心理和生理应激反应的预测因素。我们预计，报告有早期不良事件（如亲人死亡、虐待）历史的人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（如饮酒）的发病年龄较早有关，并有助于与癌症发展（如肝硬化）相关的风险因素；(2)探讨肝癌患者压力与健康行为之间的动态关系。我们预计高水平的慢性压力与(a)试图改变不良健康行为或采用适应性健康行为，或(b)试图通过持续使用或重新启动不良健康行为来减少生理唤醒有关。我们期望积极的疾病感知将调解感知压力与健康行为之间的联系，而问题聚焦应对和社会支持将调节这种关系。消极的疾病认知会调节适应不良行为以减轻压力，而情绪聚焦型应对和缺乏社会支持会调节适应不良行为的发生；(3)探讨应激、健康行为和炎症生物标志物与疾病进展的关系。我们预计，与低水平感知压力或适应性健康行为的患者相比，慢性压力和/或参与不良健康行为的患者将有异常水平的炎症生物标志物，更快的肿瘤生长和肝内和肝外转移的发展。拟议的研究是对RFA的回应，RFA要求研究将“检查中介和调节因素，如个人人口统计学（年龄、性别/性别、种族）和心理（脆弱性、复原力）差异、风险因素、早期压力暴露”。这项研究的结果有望为改善癌症患者的生活质量和降低死亡率提供潜在的心理和行为干预目标。

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. PUBLIC HEALTH RELEVANCE: 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. The life threatening and unpredictable course of cancer makes it a particularly stressful life experience; however there is great variability in reported levels of stess by those diagnosed with cancer. Perceived stress has been found to be associated with increased risk of mortality across several populations including those diagnosed with cancer. As a result, it is critical to understand the underlying mechanisms involved in the link between stress and increased risk of mortality. The goal of the proposed study will be to examine the biobehavioral pathways linking stress with cancer progression. Early life experiences (e.g., adverse events) as well as behavioral pathways (e.g., tobacco use), and their contribution on inflammation in the periphery and tumor microenvironment, will be examined in regard to disease progression. The findings of the study are expected to facilitate the development and targeting of effective interventions for those diagnosed with cancer.