The Role of Distress-Related Metabolic Dysfunction in Ovarian Cancer Development
Abstract
Ovarian cancer is the fifth leading cause of cancer death for U.S. women and the seventh most deadly cancer worldwide. Preventing ovarian cancer is challenging because, among women without genetic mutations that increase risk, it is difficult to identify women at high-risk of developing ovarian cancer. Also, although some risk factors are known, such as never giving birth and later age at menopause, they are not easy to modify. Therefore, an important area of research is discovering new risk factors that can be used to identify high-risk women so that interventions can be targeted to them. Growing evidence suggests long-term stress and distress (for example, depression and anxiety) cause changes in the body, such as increasing inflammation and suppressing the immune system, that make it more likely that a growing ovarian tumor escapes the body’s ability to eliminate it at an early stage. In our research, we found that women with depression or anxiety could be distinguished from women without depression or anxiety by the levels of certain chemicals in the blood, called metabolites. The metabolites that differed between women with and without distress also were associated with risk of ovarian cancer. We combined the various metabolites into a score, called the Metabolic Distress Score (MDS), so that we can conduct research to better understand how distress influences development of ovarian cancer. This is a potentially impactful area of research since many women have conditions of distress and interventions can be given to reduce distress. The central questions our study will address are (1) do women with more distress-related metabolites in their blood have a higher risk of being diagnosed with ovarian cancer than women with fewer distress-related metabolites? and (2) are distress-related changes in metabolites associated with characteristics in the ovarian tumor, such as markers of inflammation and poor immune function? For both study questions, we will explore whether the timing of when the MDS was measured before ovarian cancer diagnosis is important; this will provide clues into the stage of cancer development most impacted by distress. We will address the first question using data from 560 women with ovarian cancer who provided blood samples before they were diagnosed matched to 560 women without ovarian cancer who also provided blood samples. We will address the second question using data from a subset of women with ovarian cancer with both pre-diagnostic blood samples and ovarian tumor tissue. These research questions address two FY22 OCRP Areas of Emphasis: (1) Understand the basic biology and etiology of ovarian cancer initiation, progression, metastasis, recurrence, genetics and other critical events, and (2) Identify and develop new strategies for screening, early-stage detection, prevention, accurate diagnosis and prognosis. This research project is relevant to many women since conditions of distress, such as PTSD and depression, frequently develop after trauma, and trauma is a common experience among women. Exposure to trauma is particularly common among U.S. women Veterans, due to war zone exposure, combat-related injuries, military sexual trauma, and traumas experienced before enlistment. Also, over half of U.S. adult civilian women will have exposure to trauma during their lifetime. Understanding the ways distress impacts inflammation in the ovarian tumor and the body’s immune response to the tumor could lead to discovery of new targets for prevention and treatment that will be relevant for many women. Our findings will also lay the groundwork for future studies to examine whether common medications that impact metabolites, such as aspirin and statins, may help reduce risk of developing ovarian cancer among women with conditions of distress. Other types of interventions that can lower distress and distress-related metabolites, such as meditation, exercise, and healthy diet, could al
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310236
Entities
People
- Oana A Zeleznik
Organizations
- United States Army