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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA087969-15
Application #
8662725
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
15
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Li, Yanping; Pan, An; Wang, Dong D et al. (2018) Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population. Circulation 138:345-355
Liu, Ying; Colditz, Graham A; Rosner, Bernard A et al. (2018) Comparison of Performance Between a Short Categorized Lifestyle Exposure-based Colon Cancer Risk Prediction Tool and a Model Using Continuous Measures. Cancer Prev Res (Phila) 11:841-848
Sun, Qi; Zong, Geng; Valvi, Damaskini et al. (2018) Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women. Environ Health Perspect 126:037001
Rice, Megan S; Tamimi, Rulla M; Bertrand, Kimberly A et al. (2018) Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics. Breast Cancer Res Treat 170:129-141
Khawaja, Anthony P; Cooke Bailey, Jessica N; Wareham, Nicholas J et al. (2018) Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet 50:778-782
Graff, Rebecca E; Sanchez, Alejandro; Tobias, Deirdre K et al. (2018) Type 2 Diabetes in Relation to the Risk of Renal Cell Carcinoma Among Men and Women in Two Large Prospective Cohort Studies. Diabetes Care 41:1432-1437
Merritt, Melissa A; Rice, Megan S; Barnard, Mollie E et al. (2018) Pre-diagnosis and post-diagnosis use of common analgesics and ovarian cancer prognosis (NHS/NHSII): a cohort study. Lancet Oncol 19:1107-1116
Pettersson, Andreas; Gerke, Travis; Penney, Kathryn L et al. (2018) MYC Overexpression at the Protein and mRNA Level and Cancer Outcomes among Men Treated with Radical Prostatectomy for Prostate Cancer. Cancer Epidemiol Biomarkers Prev 27:201-207
Hamada, Tsuyoshi; Zhang, Xuehong; Mima, Kosuke et al. (2018) Fusobacterium nucleatum in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status. Cancer Immunol Res 6:1327-1336
Li, Bo; Wang, Yanru; Xu, Yinghui et al. (2018) Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival. Int J Cancer 142:2303-2312

Showing the most recent 10 out of 1708 publications