Pilot Study of Genetic and Psychosocial Determinants of HPA Responsivity

描述（由申请人提供）：背景：心理应激已被假设在乳腺癌病因学中发挥作用。尽管这种关系已经在几项研究中被观察到，但并没有在所有研究中得到一致的证明。造成这种差异的一个潜在原因可能是个体对压力源的生理反应不同。具体来说，压力和乳腺癌之间的因果关系得到了对压力源的生理反应的支持，这包括下丘脑-垂体-肾上腺（HPA）轴的激活，从而增加脱氢表雄酮（DHEA）及其硫酸盐（DHEAS）的分泌，这些激素在绝经后患乳腺癌的妇女中显着升高。由于心理社会、行为和基因的差异，个体对压力源的激素反应差异很大，在与疾病的关系中，个体对压力源的反应可能比压力源本身更重要。具体目的：我们长期研究的具体目的是通过特里尔社会压力测试（TSST）后血液激素的变化来确定导致HPA对急性心理压力源反应差异的遗传多态性和社会心理特征，并确定这些多态性和社会心理特征是否与乳腺癌风险相关。在这个试点研究中，我们将：1)获得管理TSST的专业知识；2)根据TSST确定我们招募研究人员的能力；3)获得HPA轴基因选择多态性携带者与非携带者以及受社会心理和环境因素影响的TSST后血中HPA激素水平变化差异的初步数据。设计：将招募40名未服用激素的绝经后妇女，并按照标准方案进行TSST。选定的HPA激素将在给予TSST之前和之后的几个时间点测量。激素对TSST的反应将根据激素峰值浓度和曲线下面积进行比较。拟议的试点研究将收集重要的初步数据，以确定乳腺癌风险增加的妇女，并使用有针对性的干预措施，削弱HPA轴对压力源的反应，从而潜在地降低乳腺癌风险。7. 拟议的试点研究将提供宝贵的初步数据，以支持一项更大、全面的研究，以检查心理社会影响对乳腺癌风险的生物学机制。从我们更大规模的研究中获得的信息可能会导致识别与她们的基因构成或社会心理特征相关的乳腺癌风险增加的女性，并可能为预防乳腺癌的干预提供目标。

DESCRIPTION (provided by applicant): 6. ABSTRACT Background: Psychological stress has been hypothesized to play a role in breast cancer etiology. Although this relationship has been observed in several studies, it has not been consistently demonstrated across studies. One potential reason for this discrepancy may be that individuals vary in their physiological response to stressors. Specifically, a causal association between stress and breast cancer is supported by the well- established physiological response to stressors, which involves activation of hypothalamic-pituitary-adrenal (HPA) axis and consequently increased secretion of dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), hormones that are significantly elevated in postmenopausal women who develop breast cancer. Individuals' hormonal responses to stressors vary considerably due to psychosocial, behavioral, and genetic differences and an individual's response to a stressor may be more important than the stressor itself in relationship to disease. Specific Aims: Specific aims of our long-term research are to identify genetic polymorphisms and psychosocial characteristics that contribute to differences in HPA responsivity to an acute psychological stressor measured by changes in blood hormones following the Trier Social Stress Test (TSST) and determine if these polymorphisms and psychosocial characteristics are associated with breast cancer risk. In this pilot study, we will: 1) obtain expertise administering the TSST; 2) determine our ability to recruit for a study based on the TSST; 3) obtain preliminary data on differences in changes in blood levels of HPA hormones following the TSST between carriers and non-carriers of selected polymorphisms in HPA axis genes and by psychosocial and environmental factors. Design: Forty postmenopausal women not taking hormones will be recruited and the TSST will be administered following a standard protocol. Selected HPA hormones will be measured at several time points before and after administering the TSST. Hormonal response to the TSST will be compared in terms of peak hormone concentrations and area under the curve. The proposed pilot study will collect important preliminary data that could lead to identification of women at increased risk for breast cancer and use of targeted interventions that blunt the HPA axis response to stressors to potentially decrease risk of breast cancer. 7. RELEVANCE TO PUBLIC HEALTH The proposed pilot study will provide valuable preliminary data to support a larger, full-scale study to examine biological mechanisms of psychosocial effects on breast cancer risk. Information learned from our larger study could lead to identification of women at increased risk of breast cancer related to their genetic make-up or psychosocial characteristics and could suggest targets for interventions to prevent breast cancer.