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..

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA087969-15
Application #
8662723
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
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 :

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