Ovarian cancer is the fifth leading cause of cancer death for U.S. women. Efforts to improve early detection have had limited success, and since few confirmed ovarian cancer risk factors are modifiable, there are few recommendations for prevention of ovarian cancer. Thus, it is critical to improve our understanding of the causes of ovarian cancer to facilitate earlier detection, as well as prevention. In recent work, we found several stress-related factors, including depression and anxiety, were associated with increased risk for developing ovarian cancer. Results from animal studies further support the hypothesis that stress can lead to higher risk for ovarian cancer, both for developing cancer in the first place and for reduced survival after onset. Post-traumatic stress disorder (PTSD) is the sentinel stress-related mental disorder, occurring in some people in response to trauma. PTSD commonly occurs among military women and, due to its significant biologic impact, it may be a particularly potent risk factor for ovarian cancer. Today, many military women experience prolonged deployments with war zone exposure, leading to combat-related injuries and trauma. As many as 21% of women Veterans of Afghanistan and Iraq and 13.1% of all Veterans accessing Veterans Administration Health Services in fiscal year 2013 have been diagnosed with PTSD. As a result, military women may also be at heightened risk for developing ovarian cancer.

Our study will evaluate whether women with versus without PTSD have higher risk of developing ovarian cancer and whether they have decreased survival after diagnosis. We will further explore possible mechanisms that could explain the relationship between PTSD and ovarian cancer risk. We will test the hypothesis that biological and behavioral processes that appear to increase risk for ovarian cancer are also more common among women with versus without PTSD. Biological factors we will consider include immune and inflammatory processes, as well as processes linked with accelerated aging. Behavioral factors we will consider include weight gain, physical inactivity, unhealthy diet, and hormone therapy use. We will also directly evaluate whether behavior-related ovarian cancer risk factors directly account for some of the association between PTSD and risk of ovarian cancer. If these processes indeed occur more commonly in women with PTSD, this will provide new insight into how and why women with PTSD are at greater risk for ovarian cancer. Such insights may then be used to develop new strategies for prevention and intervention.

Our study takes advantage of a unique resource, a long-running and ongoing cohort of over 50,000 women followed for over 25 years. Over the course of the study, investigators have obtained detailed assessments on PTSD, as well as biological and behavior-related processes, and have rigorously assessed ovarian cancer outcomes. In addition to data already collected, we can obtain novel additional biological measures that might provide new insight into mechanisms that could explain how PTSD leads to increased risk of ovarian cancer. As over 40% of patients with invasive ovarian cancer die within 3 years of diagnosis, identifying modifiable risk factors associated with ovarian cancer is critical for targeting prevention measures and, potentially, improving early detection. If women with PTSD are found to be at increased risk, increased monitoring for the purposes of early detection of subsequent physical health problems may be advisable. Examining biological and behavior-related pathways by which PTSD may lead to increased risk of ovarian cancer will identify other potential targets for prevention efforts, even among women with chronic PTSD. These biological processes and behaviors are also likely to serve as pathways linking other forms of stress to increased ovarian cancer risk, and therefore may serve as targets for intervention in women with other stress-related disorders as well.