|Grant Number:||5R01CA163451-02 Interpret this number|
|Primary Investigator:||Tworoger, Shelley|
|Organization:||Brigham And Women'S Hospital|
|Project Title:||Psychological Stress, Associate Biologic Mediators, and Ovarian Cancer Risk|
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.
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.
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.
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.
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; , .
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; , .
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; , .