PROJECT SUMMARY/ABSTRACT My ultimate goal is to become a leader in the field of cancer epidemiology who conducts innovative and high-impact research on the etiology and prevention of gynecologic cancers. Ovarian cancer is the most fatal gynecologic malignancy; despite advances in treatment, five-year survival is only 44%. The primary goal of my dissertation research is to improve ovarian cancer prevention by understanding the role of inflammation and immunity in ovarian tumor development, with a specific focus on prostaglandins. My research will leverage longitudinal questionnaire, biomarker, and tissue data from the Nurses’ Health Studies to determine how prediagnostic prostaglandin levels and long-term patterns of adult NSAID use are associated with risk of ovarian cancer. First, I will determine whether prediagnostic levels of urinary prostaglandin metabolite PGE-M are associated with risk of ovarian cancer. Second, using a lifecourse approach, I will evaluate the relationships of premenopausal and postmenopausal NSAID use with risk of ovarian cancer, considering timing, frequency, and duration of use. Third, since ovarian cancer is a highly heterogeneous disease, my proposed research will determine whether the association between NSAID use and risk of ovarian cancer differs by tumor aggressiveness or by density of tumor-associated macrophages, which are stimulated by prostaglandins. The results of this project will clarify if exposure to prostaglandins influences risk of ovarian cancer, and will provide information on the timing, frequency and duration of NSAID use that is most likely to be chemopreventive. As a postdoctoral fellow I will leverage my predoctoral training in the analysis of complex epidemiologic exposure data, ovarian tumor pathology, and biomarker research, while expanding my research to include the analysis of metabolomic and gene expression data. This training will allow me to better identify novel biomarkers and pathways in cancer etiology. Further, I will broaden my research focus to include the etiology of endometrial cancer. With this additional expertise, a growing network of collaborators, and training in grant writing, I will be well prepared to develop an innovative, multidisciplinary research program in cancer epidemiology.

PROJECT NARRATIVE Gynecologic cancers are among the most commonly diagnosed malignancies in women. Inflammation likely increases gynecologic cancer risk by release of pro-inflammatory cytokines and prostaglandins. This project will evaluate the role of prostaglandins in ovarian carcinogenesis, with potential extensions to endometrial cancer, and could identify potential targets for chemoprevention and improve prevention recommendations.