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Grant Details

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
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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.

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The Association Of Work Characteristics With Ovarian Cancer Risk And Mortality
Authors: Trudel-Fitzgerald C. , Poole E.M. , Idahl A. , Lundin E. , Sood A.K. , Kawachi I. , Kubzansky L.D. , Tworoger S.S. .
Source: Psychosomatic Medicine, 2017-03-17 00:00:00.0; , .
PMID: 28306624
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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. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2017-02-16 00:00:00.0; , .
PMID: 28209595
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Nurses' Health Study Contributions On The Epidemiology Of Less Common Cancers: Endometrial, Ovarian, Pancreatic, And Hematologic
Authors: Birmann B.M. , Barnard M.E. , Bertrand K.A. , Bao Y. , Crous-Bou M. , Wolpin B.M. , De Vivo I. , Tworoger S.S. .
Source: American Journal Of Public Health, 2016 Sep; 106(9), p. 1608-15.
PMID: 27459458
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Association Of Ovarian Tumor 2-adrenergic Receptor Status With Ovarian Cancer Risk Factors And Survival
Authors: Huang T. , Tworoger S.S. , Hecht J.L. , Rice M.S. , Sood A.K. , Kubzansky L.D. , Poole E.M. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016-09-01 00:00:00.0; , .
PMID: 27587791
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Hypertension, Use Of Antihypertensive Medications, And Risk Of Epithelial Ovarian Cancer
Authors: Huang T. , Poole E.M. , Eliassen A.H. , Okereke O.I. , Kubzansky L.D. , Sood A.K. , Forman J.P. , Tworoger S.S. .
Source: International Journal Of Cancer, 2016-07-15 00:00:00.0; 139(2), p. 291-9.
PMID: 26934358
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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. .
Source: Cancer Causes & Control : Ccc, 2016-05-10 00:00:00.0; , .
PMID: 27165168
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A Prospective Study Of Phobic Anxiety, Risk Of Ovarian Cancer, And Survival Among Patients
Authors: Poole E.M. , Kubzansky L.D. , Sood A.K. , Okereke O.I. , Tworoger S.S. .
Source: Cancer Causes & Control : Ccc, 2016-03-29 00:00:00.0; , .
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Depression, Antidepressant Use, And Postmenopausal Breast Cancer Risk
Authors: Brown S.B. , Hankinson S.E. , Arcaro K.F. , Qian J. , Reeves K.W. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Jan; 25(1), p. 158-64.
PMID: 26578537
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A Prospective Study Of Leukocyte Telomere Length And Risk Of Phobic Anxiety Among Women
Authors: Ramin C. , Wang W. , Prescott J. , Rosner B. , Simon N.M. , De Vivo I. , Okereke O.I. .
Source: Psychiatry Research, 2015-12-15 00:00:00.0; 230(2), p. 545-52.
PMID: 26603336
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Depression And Risk Of Epithelial Ovarian Cancer: Results From Two Large Prospective Cohort Studies
Authors: Huang T. , Poole E.M. , Okereke O.I. , Kubzansky L.D. , Eliassen A.H. , Sood A.K. , Wang M. , Tworoger S.S. .
Source: Gynecologic Oncology, 2015 Dec; 139(3), p. 481-6.
PMID: 26449316
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Mediterranean Diet And Telomere Length In Nurses' Health Study: Population Based Cohort Study
Authors: Crous-Bou M. , Fung T.T. , Prescott J. , Julin B. , Du M. , Sun Q. , Rexrode K.M. , Hu F.B. , De Vivo I. .
Source: Bmj (clinical Research Ed.), 2014; 349, p. g6674.
PMID: 25467028
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