In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for incident ovarian cancer. This work will use prospectively collected questionnaire data, biological samples, and paraffin-embedded ovarian tumor tissue from women in the Nurses'Health Study (NHS) and NHSII. Although several hypotheses regarding ovarian cancer etiology have been proffered, few modifiable lifestyle risk factors have been identified. We will examine the possible preventive role of vitamin D in ovarian cancer, with the goal of identifying subpopulations who could most benefit from intervention. We also will evaluate three dietary factors: flavonoids, which may reduce risk;lactose in adolescence and adulthood;and acrylamide intake and red blood cell adduct levels, both of which may increase risk. We also will evaluate the role of melatonin and shift work in ovarian carcinogenesis. In addition, we propose to measure circulating markers of inflammation (CPR, IL-6, and TNFa-R2) and tumor markers associated with inflammation (e.g., STATs). We also propose for the first time to focus specifically on fatal ovarian cancer, with an effort to identify risk factors that may predispose women to either having fast-growing tumors or a peritoneal environment susceptible to metastasis. In this same vein, we plan to evaluate hormone receptors in ovarian tumors and their relation to risk factors, with an emphasis on exploring a new model of ovarian carcinogenesis (slow-growing tumors vs. fast-growing tumors) as a way to classify tumors in epidemiologic studies. The Project shares common biological themes with Projects 1 and 2, including the role of vitamin D, melatonin, and the inflammation pathway and interacts closely with Project 4 for methodologic issues. It also shares with the other Projects a strong administrative and scientific infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis). The findings should enhance understanding of the etiology and progression of ovarian cancer and provide guidance for women and their health care providers in their efforts to reduce suffering and death from this disease.

Public Health Relevance

It is difficult to diagnose ovarian cancer, so improving prevention is key for reducing morbidity and mortality. This proposal examines potential preventive agents (vitamin D, melatonin, flavonoids) and risk factors (shiftwork, lactose, acrylamide). Another emphasis is on ovarian etiology (inflammation, hormones), which could lead to better diagnostic and treatment tools, and a focus on risk factors for fatal ovarian cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (O1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Rice, Megan S; Rosner, Bernard A; Tamimi, Rulla M (2017) Percent mammographic density prediction: development of a model in the nurses' health studies. Cancer Causes Control 28:677-684
Hanyuda, Akiko; Cao, Yin; Hamada, Tsuyoshi et al. (2017) Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status. Eur J Epidemiol 32:393-407
Irshad, Humayun; Oh, Eun-Yeong; Schmolze, Daniel et al. (2017) Crowdsourcing scoring of immunohistochemistry images: Evaluating Performance of the Crowd and an Automated Computational Method. Sci Rep 7:43286
Jiménez, M C (2017) Response to comment on plasma uric acid and risk of ischaemic stroke in women. Eur J Neurol 24:e2
Wang, Tiange; Huang, Tao; Heianza, Yoriko et al. (2017) Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain. Diabetes 66:2704-2712
Rice, Megan S; Tworoger, Shelley S; Hankinson, Susan E et al. (2017) Breast cancer risk prediction: an update to the Rosner-Colditz breast cancer incidence model. Breast Cancer Res Treat 166:227-240
Linos, E; Li, W Q; Han, J et al. (2017) Lifetime ultraviolet radiation exposure and lentigo maligna melanoma. Br J Dermatol 176:1666-1668
Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira et al. (2017) Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies. Eur J Epidemiol 32:419-430
Masugi, Yohei; Nishihara, Reiko; Hamada, Tsuyoshi et al. (2017) Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer. Cancer Immunol Res 5:1046-1055
Simon, Tracey G; King, Lindsay Y; Chong, Dawn Q et al. (2017) Diabetes, Metabolic Comorbidities and Risk of Hepatocellular Carcinoma: Results from Two Prospective Cohort Studies. Hepatology :

Showing the most recent 10 out of 1577 publications