Biobehavioral pathways linking stress and cancer progression

描述(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50万例新病例被诊断出来。癌症危及生命和不可预测的病程使它成为一种特别有压力的生活经历。压力可以被定义为施加在个人身上的要求被认为是威胁或有害的，并超过了可用于管理压力源的资源。几十年的研究表明，压力与不适应的健康行为(如高脂肪饮食)以及发病率和死亡率的增加有关。这项前瞻性研究的目的是研究慢性应激和参与不良适应健康行为与肝胆癌患者疾病进展之间的机制联系。这项拟议的研究将开始阐明在癌症的背景下，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)研究心理和生理应激反应对肝癌诊断或复发的预测作用。我们预计，报告早期不良事件(例如，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不适应健康行为(例如饮酒)的较早发病年龄有关，并导致与癌症发展相关的风险因素(例如肝硬变)；(2)检查被诊断为肝胆癌的人随着时间的推移压力与健康行为之间的动态联系。我们预计，高水平的慢性应激与(A)试图改变不良适应健康行为或采取适应性健康行为有关，或(B)试图通过继续使用或重新启动不良健康行为来降低生理唤醒。我们期望积极的疾病认知将在感受到的压力和健康行为之间起中介作用，而关注问题的应对和社会支持将调节这种关系。从事不良适应行为以减少压力将通过消极的疾病知觉来调节，并通过情绪集中的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记物在疾病进展中的联系。我们预计，与感受到的压力或适应性健康行为水平较低的患者相比，长期应激和/或参与不良健康行为的患者将具有异常水平的炎症生物标志物，以及更快的肿瘤生长和肝内外转移的发展。这项拟议的研究是对RFA的响应，RFA要求进行研究，以“检查个人人口统计(年龄、性别/性别、种族)和心理(脆弱性、韧性)差异、风险因素、早期压力暴露等中介和调节因素”。这项研究的发现有望为提高癌症患者的生活质量和降低死亡率的干预提供潜在的心理和行为目标。

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.