Grant Number:	1R01CA163451-01A1 Interpret this number
Primary Investigator:	Tworoger, Shelley
Organization:	Brigham And Women'S Hospital
Project Title:	Psychological Stress, Associate Biologic Mediators, and Ovarian Cancer Risk
Fiscal Year:	2012

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. PUBLIC HEALTH RELEVANCE: Ovarian cancer is highly fatal and there are few prevention recommendations. Characterizing the role of psychosocial stress in ovarian carcinogenesis will improve our understanding of the biology of this disease. Further, meditation, mindfulness, and yoga can reduce perceived stress and its biologic effects. These safe, low-cost behavioral interventions could provide new prevention strategies for this deadly disease.




Plasma and ovarian metabolomic responses to chronic stress in female mice.
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EPub date: 2025-07-01 00:00:00.0.
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Caregiver burden and risk of epithelial ovarian cancer in the Nurses' Health Studies.
Authors: Barnard M.E. , Poole E.M. , Huang T. , Sood A.K. , Kubzansky L.D. , Tworoger S.S. .
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Fulfilled mind, healthy gut? Relationships of eudaimonic psychological well-being with the gut microbiome in postmenopausal women.
Authors: Guimond A.J. , Ke S. , Tworoger S.S. , Huang T. , Chan A.T. , Kubzansky L.D. , Liu Y.Y. .
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Plasma metabolomic signature of early abuse in middle-aged women.
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Antihypertensive medication use and ovarian cancer survival.
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Religion, spirituality and diurnal rhythms of salivary cortisol and dehydroepiandrosterone in postmenopausal women.
Authors: Isehunwa O.O. , Warner E.T. , Spiegelman D. , Huang T. , Tworoger S.S. , Kent B.V. , Shields A.E. .
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Prolactin and Risk of Epithelial Ovarian Cancer.
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Habitual sleep quality, plasma metabolites and risk of coronary heart disease in post-menopausal women.
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Variation in DNA methylation of human blood over a 1-year period using the Illumina MethylationEPIC array.
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Circulating prolactin concentrations and risk of type 2 diabetes in US women.
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Stability and reproducibility of proteomic profiles measured with an aptamer-based platform.
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Prediagnosis Leukocyte Telomere Length And Risk Of Ovarian Cancer
Authors: Yang M. , Prescott J. , Poole E.M. , Rice M.S. , Kubzansky L.D. , Idahl A. , Lundin E. , De Vivo I. , Tworoger S.S. .
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Association of Ovarian Tumor ß2-Adrenergic Receptor Status with Ovarian Cancer Risk Factors and Survival.
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Antidepressant use and circulating prolactin levels.
Authors: Reeves K.W. , Okereke O.I. , Qian J. , Tworoger S.S. , Rice M.S. , Hankinson S.E. .
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Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study.
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A prospective study of phobic anxiety, risk of ovarian cancer, and survival among patients.
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A prospective study of leukocyte telomere length and risk of phobic anxiety among women.
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Depression and risk of epithelial ovarian cancer: Results from two large prospective cohort studies.
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