We propose to continue the follow-up of 116,678 women who in 1989 were enrolled in the prospective Nurses'Health Study II (NHSII) to identify potentially modifiable determinants of breast cancer risk in young women. In this unique cohort, exposure information has been collected at two-year intervals beginning when women were 25-42 years of age. Active response to follow-up questionnaires has been approximately 90% and ascertainment of deaths is virtually complete;through 2011 we expect 4023 incident cases of invasive breast cancer. Since 1989, we have collected plasma, DNA, red blood cells, and urine samples from participants;already these resources have provided many new insights on factors that influence the incidence of premenopausal breast cancer. Our proposed specific aims build upon the extensive exposure information collected during premenopausal years and substantially extend the original objectives. Specifically, we will evaluate whether associations we have seen with high school and premenopausal adult diet, adolescent physical activity, shift work, and melatonin secretion also influence risk of postmenopausal breast cancer. To assess potential underlying mechanisms for an association we observed with consumption of red meat, we will evaluate the relation of plasma ferritin to risk of breast cancer. Further we will assess whether specific carotenoids, and plasma enterolactone predict risk. We will also evaluate whether the associations that we observe between modifiable factors and risk of breast cancer are accounted for by increased mammographic density. We will use emerging results from genome wide association studies (GWAS) to construct a genetic risk score based on the collective effects of multiple polymorphisms with established links to breast cancer;among women at higher genetic risk we evaluate the potential for risk reduction by the modifiable risk factors that we have identified. We will also use the information on traditional and novel risk factors, plasma hormone levels, mammographic density, and the genetic risk score that will be available in NHSII to create a new prediction model for premenopausal breast cancer specifically and also for postmenopausal breast cancer using exposures ascertained before menopause in addition to traditional risk factors determined after menopause. This breadth of information should substantially outperform available models and identify individual women at high risk for focused research and, potentially, preventive interventions. The results of the proposed aims will continue to provide new information on the origins of premenopausal and postmenopausal breast cancer;and on modifiable risk factors. In addition to these specific aims, the follow-up of the NHSII cohort provides a key source of data and biological specimens from young women that are used by multiple consortia and collaborations, and that provide the foundation for many ancillary studies related to women's health.

Public Health Relevance

We propose to continue the follow-up of 116,678 women, initially 25 to 42 years of age when recruited in 1989, in the Nurses'Health Study II. We will assess the risk of breast cancer in pre and post menopausal women through an evaluation of dietary and lifestyle factors during adolescence and early adult life, biomarkers that reflect dietary factors, mammographic density, and a new genetic risk score. Already, this study has identified multiple potentially modifiable risk factors for breast cancer in young women, and the extended follow-up should provide further information on the prevention of this and other important diseases.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Mahabir, Somdat
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Public Health
United States
Zip Code
Oh, Hannah; Boeke, Caroline E; Tamimi, Rulla M et al. (2015) The interaction between early-life body size and physical activity on risk of breast cancer. Int J Cancer 137:571-81
Tong, L X; Wu, S; Li, T et al. (2015) Personal history of gallstones and risk of incident psoriasis and psoriatic arthritis in U.S. women. Br J Dermatol 172:1316-22
Wu, Shaowei; Han, Jiali; Qureshi, Abrar A (2015) Use of aspirin, non-steroidal anti-inflammatory drugs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis: a cohort study. Acta Derm Venereol 95:217-23
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
Su, Xuefen; Boeke, Caroline E; Collins, Laura C et al. (2015) Intakes of fat and micronutrients between ages 13 and 18 years and the incidence of proliferative benign breast disease. Cancer Causes Control 26:79-90
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
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
Dougan, M M; Willett, W C; Michels, K B (2015) Prenatal vitamin intake during pregnancy and offspring obesity. Int J Obes (Lond) 39:69-74
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
Mahalingaiah, Shruthi; Hart, Jaime E; Laden, Francine et al. (2014) Air pollution and risk of uterine leiomyomata. Epidemiology 25:682-8

Showing the most recent 10 out of 409 publications