Ovarian cancer is the fifth leading cause of cancer death for women in the United States and the seventh most fatal worldwide. Unfortunately, we currently do not have a complete understanding of the causes of ovarian cancer, and thus do not have good strategies for preventing ovarian cancer or detecting it at early stages. Therefore, identifying modifiable risk factors for ovarian cancer is important for improving our ability to prevent this deadly disease.

Psychological stress has recently been proposed as a risk factor for ovarian cancer. Psychological stress refers to the emotional and physiological reactions experienced when a woman is confronted by a situation that has demands that go beyond her coping resources. Examples of stressful situations are marital issues, death of a loved one, or health problems. Many stressful events are short-term, but can lead to long-term chronic stress. When a woman has chronic stress, her body releases stress hormones that can alter the immune system and may directly impact cancer development. In mice, chronic stress causes larger and more aggressive ovarian cancers, but is unclear whether stress may act the same way in humans. Given that chronic stress is common and treatable, it should be evaluated as a potential risk factor for ovarian cancer. This will help us identify groups of women who may be at high risk of getting ovarian cancer and could benefit from more screening. Further, we could design better strategies for prevention that target these women.

In this study, I will examine whether stress is related to ovarian cancer in a variety of ways. First, in the Nurses' Health Study (NHS) and NHSII, two large studies of over 100,000 women each, women have reported on stress due to phobias (i.e., fear of heights), symptoms of depression, job stress, caregiving stress, and having low social support. I will test whether any of these sources of stress are more common among women who developed ovarian cancer compared to women who did not develop ovarian cancer. Second, because we could not ask about all possible sources of stress in these women, I will develop a blood marker (i.e., a signature) of chronic stress exposure in the NHS and NHSII. To do this, I will use metabolomic profiling. Metabolomic profiling measures many of the proteins, amino acids, lipids, and other substances that the body uses in its chemical processes. Many of these metabolites are known to be affected by chronic stress. To create a chronic stress signature, I will measure the metabolome in women with and without post-traumatic stress disorder (PTSD), a condition associated with high levels of chronic stress, and compare their metabolomic profiles. Once I identify which metabolites are important for distinguishing between women with and without PTSD (i.e., the stress signature), I will examine those metabolites in women with and without ovarian cancer to see whether the stress signature is more common in women with ovarian cancer than women without cancer.

My career goals are to improve ovarian cancer prevention, understand the biology of ovarian cancer by taking into account the multiple ways in which ovarian cancer develops, and to improve ovarian cancer survival and quality of life. My research and training plan accomplishes these goals by investigating chronic stress and risk of ovarian cancer. This research directly addresses my career goals in the following ways. First, if chronic stress is linked to ovarian cancer in humans, then we can potentially improve prevention by means of stress reduction techniques. Second, if stress is a risk factor for ovarian cancer, this would be a new pathway of ovarian cancer development; future research would be needed to understand the ways in which stress leads to ovarian cancer. Third, ovarian cancer patients are highly stressed; therefore, stress reduction techniques may be an important way of helping these women to cope with their diagnoses and improve their quality of life.

The potential clinical benefits of this research include improving ovarian cancer prevention recommendations. Given that there are no known prevention recommendations or early detection methods for all women, stress reduction has the potential to substantially improve prevention recommendations. Furthermore, since stress reduction techniques do not involve medications, the potential for adverse side effects is limited. Additionally, stress reduction has benefits in terms of other chronic diseases, such as cardiovascular disease, which may provide more incentive for women to participate in this type of activity. In total, the study of stress in ovarian cancer has great potential to improve prevention as well as further our understanding of how ovarian cancer develops.