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.
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.
|Jung, Seungyoun; Allen, Naomi; Arslan, Alan A et al. (2017) Demographic, lifestyle, and other factors in relation to antimüllerian hormone levels in mostly late premenopausal women. Fertil Steril 107:1012-1022.e2|
|Lindström, Sara; Finucane, Hilary; Bulik-Sullivan, Brendan et al. (2017) Quantifying the Genetic Correlation between Multiple Cancer Types. Cancer Epidemiol Biomarkers Prev 26:1427-1435|
|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; 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|
|Harris, Holly R; Willett, Walter C; Vaidya, Rita L et al. (2017) An Adolescent and Early Adulthood Dietary Pattern Associated with Inflammation and the Incidence of Breast Cancer. Cancer Res 77:1179-1187|
|Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan et al. (2017) Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. Br J Cancer 116:524-535|
|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|
|Beca, Francisco; Kensler, Kevin; Glass, Benjamin et al. (2017) EZH2 protein expression in normal breast epithelium and risk of breast cancer: results from the Nurses' Health Studies. Breast Cancer Res 19:21|
|Hu, Yang; Cui, Jing; Sparks, Jeffrey A et al. (2017) Circulating carotenoids and subsequent risk of rheumatoid arthritis in women. Clin Exp Rheumatol 35:309-312|
|Liu, Ying; Tamimi, Rulla M; Colditz, Graham A et al. (2017) Alcohol consumption across the life course and mammographic density in premenopausal women. Breast Cancer Res Treat :|
Showing the most recent 10 out of 559 publications