Pilot Study of Genetic and Psychosocial Determinants of HPA Responsivity

描述（由申请人提供）：6。摘要背景：心理压力已被假设在乳腺癌病因中发挥作用。虽然在几项研究中观察到了这种关系，但在不同的研究中并没有一致的证明。这种差异的一个潜在原因可能是个体对压力的生理反应不同。具体而言，压力和乳腺癌之间的因果关系得到了对压力源的充分确立的生理反应的支持，其涉及下丘脑-垂体-肾上腺（HPA）轴的激活，并因此增加脱氢表雄酮（DHEA）及其硫酸盐（DHEAS）的分泌，脱氢表雄酮及其硫酸盐是在发展乳腺癌的绝经后妇女中显著升高的激素。个体对压力源的激素反应由于心理社会、行为和遗传差异而变化很大，个体对压力源的反应可能比压力源本身与疾病的关系更重要。具体目标：我们长期研究的具体目标是确定遗传多态性和心理社会特征，这些遗传多态性和心理社会特征有助于HPA对急性心理应激源的反应差异，通过特里尔社会应激试验（TSST）后血液激素的变化来测量，并确定这些多态性和心理社会特征是否与乳腺癌风险相关。在这项初步研究中，我们将：1）获得管理TSST的专业知识; 2）确定我们招募基于TSST的研究的能力; 3）获得关于HPA轴基因中选定多态性的携带者和非携带者之间TSST后HPA激素血液水平变化差异的初步数据，以及心理社会和环境因素。设计：将招募40名未服用激素的绝经后妇女，并按照标准方案给予TSST。将在TSST给药前后的几个时间点测量选定的HPA激素。将根据峰值激素浓度和曲线下面积比较对TSST的激素反应。拟议的试点研究将收集重要的初步数据，这些数据可能会导致识别乳腺癌风险增加的女性，并使用有针对性的干预措施，削弱HPA轴对压力源的反应，从而可能降低乳腺癌的风险。7.与公共卫生的相关性拟议的试点研究将提供有价值的初步数据，以支持一个更大的，全面的研究，以检查乳腺癌风险的心理社会影响的生物学机制。从我们更大规模的研究中了解到的信息可能会导致识别出与其遗传组成或心理社会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措施提出目标。

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.