Pilot Study of Genetic and Psychosocial Determinants of HPA Responsivity

HPA 反应性的遗传和社会心理决定因素的初步研究

• 批准号: 7388500
• 负责人: JOANNE F DORGAN
• 金额: $ 8.55万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7388500
• 关键词: Acute; Adrenal Glands; Adrenal hormone preparation; Affect; Aminobutyric Acid; Aminobutyric Acids; Area Under Curve; Behavioral; Behavioral Genetics; Biological; Blood; CYP21A2 gene; Cancer Etiology; Characteristics; Condition; Corticotropin; Corticotropin Receptors; Corticotropin-Releasing Hormone; Data; Disease; Environment; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Event; Genes; Genetic; Genetic Polymorphism; Glucocorticoid Receptor; Grant; Hormonal; Hormones; Hydrocortisone; Hypothalamic structure; Individual; Individual Differences; Inorganic Sulfates; Intervention; Lead; Learning; Life; Measures; Physiological; Pilot Projects; Pituitary Gland; Play; Postmenopause; Preparation; Prospective Studies; Protocols documentation; Psychological Stress; Public Health; Receptor Gene; Recruitment Activity; Research; Risk; Role; Serum; Social support; Socioeconomic Status; Spouses; Standards of Weights and Measures; Stress; Sympathetic Nervous System; Time; Treatment/Psychosocial Effects; Trier Social Stress Test; Unspecified or Sulfate Ion Sulfates; Variant; Woman; Work; abstracting; base; cancer risk; coping; dehydroepiandrosterone; design; experience; hypothalamic-pituitary-adrenal axis; malignant breast neoplasm; prevent; programs; prospective; psychologic; psychological stressor; psychosocial; receptor; response; stressor

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.

描述（由申请人提供）： 6. 摘要背景：假设心理压力在乳腺癌病因学中发挥作用。尽管在多项研究中都观察到了这种关系，但在不同的研究中并未得到一致的证明。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有所不同。具体来说，压力与乳腺癌之间的因果关系得到了对压力源的明确生理反应的支持，该反应涉及下丘脑-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，这些激素在患乳腺癌的绝经后妇女中显着升高。由于社会心理、行为和遗传差异，个体对压力源的激素反应差异很大，并且在与疾病的关系中，个体对压力源的反应可能比压力源本身更重要。具体目标：我们长期研究的具体目标是确定导致 HPA 对急性心理压力源（通过特里尔社会压力测试 (TSST) 后血液激素变化来测量）反应性差异的遗传多态性和心理社会特征，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 确定我们招募研究对象的能力； 3) 获得关于HPA轴基因中选定的多态性携带者和非携带者之间的TSST后HPA激素血液水平变化的差异以及社会心理和环境因素的初步数据。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。将在施用 TSST 之前和之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来比较对 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来减弱 HPA 轴对压力源的反应，从而可能降低患乳腺癌的风险。 7. 与公众健康的相关性 拟议的试点研究将提供有价值的初步数据，以支持更大规模的全面研究，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出与其基因构成或社会心理特征相关的乳腺癌风险增加的女性，并可能提出预防乳腺癌的干预措施的目标。