In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for incident and fatal breast cancer, including those that affect survival after the diagnosis of breast cancer. This work will use the stored blood and urine samples, archived DNA, repeated questionnaires, and long follow-up in the Nurses'Health Study (1976- 2012 with approximately 10,000 incident invasive breast cancers). Exposures will also be related to tumor characteristics using pathology blocks from incident breast cancers. We will specifically examine the relation of vitamin D and melatonin to breast cancer risk, intakes and blood levels of 1-carbon nutrients to risk of breast cancers characterized by global hypomethylation (assessed by LINE-1 methylation), and change in alcohol consumption to breast cancer incidence. We will also assess risk factors in relation to tumors classified by expression of multiple receptors and in relation to fatal breast cancer. The association of modifiable factors to risk of breast cancer will be examined among women at elevated genetic risk defined by ongoing GWAS's. LINE-1 methylation of breast cancers will be evaluated as an independent prognostic factor, and the possibility that low physical activity and greater weight reduce survival through the insulin signaling pathway will be examined. Post diagnostic dietary insulin index and protein quality will be evaluated as predictors of survival. This Project shares common biological and mechanistic themes with Projects 2, and 3, including the role of vitamin D, 1-carbon metabolism, and energy balance in relation to cancer incidence and survival, and like the other Projects interacts closely with Project 4 for methodological 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 breast 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

We propose to identify additional nutritional and hormonal risk factors for breast cancer incidence and survival. We will continue to follow the 121,700 women in the Nurses'Health Study, who since 1976 have provided detailed information on lifestyle factors, and cancer diagnoses;many also provided blood and urine samples. Our findings are likely to provide additional information on ways to reduce suffering and death due to breast cancer..

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-7)
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
Sparks, Jeffrey A; Chen, Chia-Yen; Jiang, Xia et al. (2015) Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history. Ann Rheum Dis 74:1522-9
Ananthakrishnan, Ashwin N; Du, Mengmeng; Berndt, Sonja I et al. (2015) Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies. Cancer Epidemiol Biomarkers Prev 24:198-205
Tworoger, Shelley S; Rice, Megan S; Rosner, Bernard A et al. (2015) Bioactive prolactin levels and risk of breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 24:73-80
Song, Mingyang; Gong, Jian; Giovannucci, Edward L et al. (2015) Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer 137:154-64
Merola, Joseph F; Wu, Shaowei; Han, Jiali et al. (2015) Psoriasis, psoriatic arthritis and risk of gout in US men and women. Ann Rheum Dis 74:1495-500
Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko et al. (2015) Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. Ann Surg Oncol 22:1226-35
Bertrand, Kimberly A; Rosner, Bernard; Eliassen, A Heather et al. (2015) Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer. Breast Cancer Res Treat 149:479-87
Lopez-Garcia, Esther; Rodriguez-Artalejo, Fernando; Li, Tricia Y et al. (2014) The Mediterranean-style dietary pattern and mortality among men and women with cardiovascular disease. Am J Clin Nutr 99:172-80
Zhou, Jiachen; Kelsey, Karl T; Giovannucci, Edward et al. (2014) Fluid intake and risk of bladder cancer in the Nurses' Health Studies. Int J Cancer 135:1229-37
Li, Shanshan; Flint, Alan; Pai, Jennifer K et al. (2014) Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study. BMJ 348:g2659

Showing the most recent 10 out of 1102 publications