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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA163451-04
Application #
8918515
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Green, Paige A
Project Start
2012-09-13
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
4
Fiscal Year
2015
Total Cost
$412,105
Indirect Cost
$132,535
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Trudel-Fitzgerald, Claudia; Tworoger, Shelley S; Poole, Elizabeth M et al. (2018) Psychological symptoms and subsequent healthy lifestyle after a colorectal cancer diagnosis. Health Psychol 37:207-217
Li, Jun; Rice, Megan S; Huang, Tianyi et al. (2018) Circulating prolactin concentrations and risk of type 2 diabetes in US women. Diabetologia 61:2549-2560
Mons, Ute; Müezzinler, Aysel; Schöttker, Ben et al. (2017) Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies. Am J Epidemiol 185:1317-1326
Yang, Meng; Prescott, Jennifer; Poole, Elizabeth M et al. (2017) Prediagnosis Leukocyte Telomere Length and Risk of Ovarian Cancer. Cancer Epidemiol Biomarkers Prev 26:339-345
Trudel-Fitzgerald, Claudia; Poole, Elizabeth M; Idahl, Annika et al. (2017) The Association of Work Characteristics With Ovarian Cancer Risk and Mortality. Psychosom Med 79:1059-1067
Huang, Tianyi; Poole, Elizabeth M; Vetter, Celine et al. (2017) Habitual sleep quality and diurnal rhythms of salivary cortisol and dehydroepiandrosterone in postmenopausal women. Psychoneuroendocrinology 84:172-180
Huang, Tianyi; Tworoger, Shelley S; Hecht, Jonathan L et al. (2016) Association of Ovarian Tumor ?2-Adrenergic Receptor Status with Ovarian Cancer Risk Factors and Survival. Cancer Epidemiol Biomarkers Prev 25:1587-1594
Reeves, Katherine W; Okereke, Olivia I; Qian, Jing et al. (2016) Antidepressant use and circulating prolactin levels. Cancer Causes Control 27:853-61
Huang, Tianyi; Poole, Elizabeth M; Eliassen, A Heather et al. (2016) Hypertension, use of antihypertensive medications, and risk of epithelial ovarian cancer. Int J Cancer 139:291-9
Poole, Elizabeth M; Kubzansky, Laura D; Sood, Anil K et al. (2016) A prospective study of phobic anxiety, risk of ovarian cancer, and survival among patients. Cancer Causes Control 27:661-8

Showing the most recent 10 out of 15 publications