Psychological stress, associate biologic mediators, and ovarian cancer risk

心理压力、相关生物介质和卵巢癌风险

• 批准号: 8545123
• 负责人: Shelley S Tworoger
• 金额: $ 38.9万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-13 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545123
• 关键词: Address; Adrenergic Receptor; Adrenergic beta-Antagonists; Animal Model; Animals; Anxiety; Area; Behavior Therapy; Biological; Biological Markers; Biology; Blood; Blood specimen; Cancer Etiology; Caregiver Burden; Cessation of life; Chronic; Chronic stress; Cohort Studies; Collaborations; Cross-Sectional Studies; DNA; Data; Development; Diagnosis; Diagnostic; Dimensions; Disease; Early Diagnosis; Epithelial ovarian cancer; Etiology; Evaluation; Event; Family history of; Gelatinase A; Health; High Risk Woman; Human; Incidence; Individual; Intervention; Lead; Length; Malignant neoplasm of ovary; Matrix Metalloproteinases; Measures; Mediator of activation protein; Meditation; Metric; Modeling; Mus; New York; Nurses' Health Study; Occupations; Ovarian; Oxytocin; Pathway interactions; Patients; Pharmaceutical Preparations; Physicians; Plasma; Prevention; Prevention Measures; Prevention strategy; Primary Prevention; Prolactin; Prospective Studies; Psychological Stress; Psychosocial Stress; Questionnaires; Recommendation; Research; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Serous; Small Interfering RNA; Social isolation; Source; Specimen; Staging; Stress; Sweden; Telomere Shortening; Time; Translating; Universities; Up-Regulation; Woman; Women' s Health; Yoga; base; biological adaptation to stress; cancer risk; carcinogenesis; caregiving; cohort; cost; depressive symptoms; disorder risk; follow-up; high risk; improved; innovation; malignant breast neoplasm; mindfulness meditation; modifiable risk; mortality; mouse model; novel; ovarian cancer prevention; ovarian neoplasm; prevent; prospective; psychological distress; psychosocial; research study; stressor; success; telomere; tumor; tumor growth

DESCRIPTION (provided by applicant): Ovarian cancer is the fifth most common cause of cancer death among women, in part due to the existence of aggressive subtypes and few prevention recommendations. Thus, the identification of modifiable risk factors is critical to target prevention and elucidate the biology of ovarian cancer. In an ovarian cancer mouse model, animals under chronic stress had larger and more aggressive tumors than controls. Stress acted through the ¿2-adrenergic receptor and increased expression of MMPs. In this highly translational application, we propose to investigate the association of validated metrics of psychosocial stress, including psychological distress (anxiety, depressive symptoms) and psychosocial stressors (care-giving stress, job strain, social isolation), with risk of ovarian cancer in over 950 prospectively-collected cases from the Nurses' Health Study cohorts (NHS and NHSII). We hypothesize that stress will be most strongly associated with aggressive tumors. Beta blocker medications block the ¿2-adrenergic receptor, a centerpiece of the stress pathway, and thus may be associated with a reduced ovarian cancer risk, particularly among those with high stress. Further, a number of biologic mediators of the stress response have been identified, including MMP-2, prolactin, oxytocin, and telomere length. We propose to evaluate these biomarkers with disease risk in prospectively-collected plasma samples from 662 ovarian cancer cases within the NHS, NHSII, the Women's Health Study, the New York University Women's Health Study, and the Northern Sweden Health and Disease Study. With the large sample size, detailed follow-up and available blood and DNA specimens, our study provides a unique opportunity to conduct the first prospective assessment of a novel mechanism of ovarian carcinogenesis. Understanding whether psychosocial stress is related to ovarian cancer risk will elucidate key carcinogenic pathways. Further, this research could lead to substantial improvements in prevention, since behavioral interventions (e.g., yoga) can reduce perceived stress. This innovative application will translate experimental research into prospective human studies and potentially could improve our understanding of ovarian carcinogenesis and our ability to prevent this fatal disease.

描述（由适用提供）：卵巢癌是女性癌症死亡的第五大最常见原因，部分原因是存在着侵略性亚型和很少的预防建议。这是对可修改风险因素的识别对于靶向预防和阐明卵巢癌的生物学至关重要。在卵巢癌小鼠模型中，慢性应激下的动物比对照组更大，更具侵略性的肿瘤。通过2-肾上腺素受体和MMP表达增加的应力。在这个高度翻译的应用中，我们建议调查经过验证的指标的关联 社会心理压力，包括心理困扰（焦虑，抑郁症状）和社会心理压力源（护理压力，工作压力，社会隔离），以及来自护士健康研究队列（NHS和NHSII）的950例前瞻性预期病例的卵巢癌风险。我们假设压力将与侵袭性肿瘤最密切相关。 β受体阻滞剂的药物阻断了2-肾上腺素受体，这是应力途径的核心，因此可能与卵巢癌的风险降低有关，尤其是在高应激的癌症风险中。此外，已经确定了许多应力反应的生物介质，包括MMP-2，催乳素，催产素和端粒长度。我们建议在NHS中662例卵巢癌病例的前瞻性血浆样本中评估这些具有疾病风险的生物标志物，NHSII，妇女健康研究，纽约大学妇女健康研究和瑞典北部的健康与疾病研究。我们的研究凭借大量样本量，详细的随访以及可用的血液和DNA标本，提供了一个独特的机会，可以对卵巢癌的新机理进行首次前瞻性评估。了解心理压力是否与卵巢癌风险有关，是否会阐明关键的致癌途径。此外，由于行为干预（例如瑜伽）可以减轻感知的压力，因此这项研究可能会导致预防的重大改善。这种创新的应用将将实验研究转化为前瞻性人类研究，并有可能提高我们对卵巢癌发生的理解以及我们预防这种致命疾病的能力。