We propose to continue the follow-up of the Nurses'Health Study II, a cancer epidemiology cohort of 116,430 women enrolled at ages 25 to 42 years in 1989. The cohort is currently supported as an R0I. Consistent with NCI policy, we are now applying for support of the infrastructure through a cooperative agreement. The NHSII biorepository includes plasma, red blood cells, white blood cells, and first morning urine samples from 29,611 women;for two thirds of these women we have timed follicular and luteal premenopausal samples. Over 16,000 provided a 2nd blood/urine sample in 2008-11 when the majorities were postmenopausal, and we have cheek cell DNA from an additional 29,859 women. We have collected archival tissue blocks for incident breast and ovarian cancers and melanoma (approximately 70% of requested have been obtained). We have created tissue microarrays for breast cancers that are already being used extensively. Prediagnostic mammograms have been collected for breast cancer cases and controls, as well as pathology material from previous biopsies of benign lesions. The follow-up of the NHSII cohort, conducted every two years, has been high and accounts for 93% of potential person-time. We have nearly complete ascertainment of deaths using the National Death Index and other methods. The NHSII cohort is unique in many ways, as the only large cohort of women enrolled before menopause, with information on smoking, weight, medication use, and medical diagnoses updated every 2 years and information on diet and physical activity updated every four years. Further, we have collected detailed on in utero and infant exposures (from participants'mothers), diet during high school, and other valuable exposure information. This cohort has been highly productive;over 150 papers have been published during the last five years, and the rate of publication is increasingly rapidly. This cohort is a member of the NCI Cohort Consortium, has participated in many collaborative studies, and has an active resource-sharing component. Enhancements of the cohort infrastructure involve assessment of breast tumor DNA methylation and RNA expression and the gut microbiome, and development of software to account for measurement error.

Public Health Relevance

The goal is to continue the follow-up of the NHSII, a cohort of women with repeated, cycle timed biomarkers and measures of diet, physical activity, and other exposures over several decades. Cohort follow-up is reaching the most informative phase and is a unique resource for scientific aims that integrate diet, other lifestyle variables, biomarkers, genetic predisposition and mediating variables in relation to cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZCA1)
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Mahabir, Somdat
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Harvard University
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Poole, Elizabeth M; Lin, Wayne T; Kvaskoff, Marina et al. (2017) Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses. Cancer Causes Control 28:437-445
Hu, Yang; Sparks, Jeffrey A; Malspeis, Susan et al. (2017) Long-term dietary quality and risk of developing rheumatoid arthritis in women. Ann Rheum Dis 76:1357-1364
Milne, Roger L (see original citation for additional authors) (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49:1767-1778
Drucker, Aaron M; Li, Wen-Qing; Park, Min Kyung et al. (2017) Niacin intake and incident adult-onset atopic dermatitis in women. J Allergy Clin Immunol 139:2020-2022.e2
Reeves, Katherine W; Okereke, Olivia I; Qian, Jing et al. (2017) Depression, antidepressant use and breast cancer risk in pre- and postmenopausal women: a prospective cohort study. Cancer Epidemiol Biomarkers Prev :
Khalili, Hamed; de Silva, Punyanganie S; Ananthakrishnan, Ashwin N et al. (2017) Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis. Inflamm Bowel Dis 23:1088-1095
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
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
Farland, Leslie V; Mu, Fan; Eliassen, A Heather et al. (2017) Menstrual cycle characteristics and steroid hormone, prolactin, and growth factor levels in premenopausal women. Cancer Causes Control 28:1441-1452
Sapkota, Yadav; Vivo, Immaculata De; Steinthorsdottir, Valgerdur et al. (2017) Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry. Sci Rep 7:11380

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