Lauren King

B.A.

NCI-DCEG

Medical Research Scholar Program Fellow

PLCO (Learn more about this study)

PLCO-576

Jan 30, 2020

Evaluating existing data on circulating inflammatory markers in relation to history of benign gynecologic pathology and history of oral contraceptive use.

Benign gynecologic pathology is very common in the US. An estimated 20-50% of women in the US have symptomatic uterine fibroids. Fibroids are considered local sites of angiogenic, hormonal, and inflammatory activity within the uterus and for many women, are characterized by pain and vaginal bleeding. Moreover, 10-15% of reproductive-aged women are estimated to have symptomatic endometriosis. It has largely been known that endometriosis is a disease of chronic inflammation caused by ectopic endometrial implants and stroma outside the uterine cavity. Implants are commonly found in the ovaries and peritoneum but have also been shown to spread systemically to distant locations, such as the lungs and soft tissue. NSAIDs are the first-line treatment for symptomatic fibroids and endometriosis, which further supports the existence of an inflammatory state associated with these pathologies. The systemic nature of these local inflammatory pathologies are currently unknown. Furthermore, oral contraceptives (OCs) are commonly used in the treatment of these pathologies and known to have effects on circulating inflammatory markers and cancer risk.

There is evidence that chronic systemic and local inflammation is associated with cancer risk. The body’s immune reaction is tightly linked with the development of many cancers, including endometrial and ovarian cancer. In the case of endometriosis, large cohort studies have confirmed that endometriosis is an independent risk factor for ovarian cancer, but associations between cancer and fibroids and other benign pathology are less clear. Often cancer risk is directly associated with the organ affected by inflammation, but in the case of systemic inflammation, there may be multiple sites at increased risk.

Systemic inflammatory markers are associated with increased endometrial and ovarian cancer risks. Prior studies by our group using PLCO data found that SERPINE1 and VEGFA are positively associated with endometrial cancer while CCL3, IL13, IL21, IL1b and IL23 are inversely associated with endometrial cancer. Additionally, CRP, IL1a, IL8 and TNFa have been positively associated with ovarian cancer risk. Meanwhile, 5-year use of OCs has been known to decrease ovarian cancer risk 30-50 years following cessation and the Nurses’ Health Study found that 5-year use of OCs decreased circulating inflammatory markers for both premenopausal and postmenopausal women. This project will allow us to understand whether certain benign conditions are also associated with inflammatory markers linked to cancer risk.

Therefore, we propose to utilize the questionnaire data collected from PLCO that captured information on history of benign gynecologic pathology and history of OC use, along with existing serum measurements of inflammatory markers to determine relationships to alterations in inflammatory markers.

Primary Aim: To determine if history of benign gynecologic pathologies (benign ovarian tumor/cyst, endometriosis, uterine fibroids) are correlated with circulating levels of systemic inflammatory markers.

We hypothesize that women with history of benign gynecologic pathologies, particularly endometriosis, will have increased systemic inflammatory marker levels.

Secondary Aim: To determine if history of oral contraceptive use is correlated with circulating levels of systemic inflammatory markers.

We hypothesize that women with history of OC use will have decreased systemic inflammatory marker levels as compared to non-users.

To conduct this study in the largest study population possible we would like to combine questionnaire and circulating inflammatory data from the six study populations (non-Hodgkin lymphoma, ovarian cancer, endometrial cancer, colorectal cancer and the 2 lung cancer studies). Previously, weights were created by Information Management Services (IMS) for the non-Hodgkin lymphoma, ovarian and first lung cancer studies. We will need to work with IMS to create relevant weights for the endometrial, colorectal and second lung cancer studies.