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Grant Details

Grant Number: 5R01CA050385-24 Interpret this number
Primary Investigator: Willett, Walter
Organization: Harvard University (Sch Of Public Hlth)
Project Title: Risk Factors for Breast Cancer in Younger Nurses
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): 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.

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Publications

Women's experience of abuse in childhood and their children's smoking and overweight.
Authors: Roberts AL, Galea S, Austin SB, Corliss HL, Williams MA, Koenen KC
Source: Am J Prev Med, 2014 Mar;46(3), p. 249-58.
PMID: 24512863
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Muscle-strengthening and conditioning activities and risk of type 2 diabetes: a prospective study in two cohorts of US women.
Authors: Grøntved A, Pan A, Mekary RA, Stampfer M, Willett WC, Manson JE, Hu FB
Source: PLoS Med, 2014 Jan;11(1), p. e1001587.
EPub date: 2014 Jan 14.
PMID: 24453948
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Pigmentary traits, family history of melanoma and the risk of endometriosis: a cohort study of US women.
Authors: Kvaskoff M, Han J, Qureshi AA, Missmer SA
Source: Int J Epidemiol, 2014 Feb;43(1), p. 255-63.
PMID: 24343850
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Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case-control study.
Authors: Arkema EV, Goldstein BL, Robinson W, Sokolove J, Wagner CA, Malspeis S, Rosner B, Grodstein F, Karlson EW, Costenbader KH
Source: Arthritis Res Ther, 2013 Oct 23;15(5), p. R159.
EPub date: 2013 Oct 23.
PMID: 24286474
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The weight of traumatic stress: a prospective study of posttraumatic stress disorder symptoms and weight status in women.
Authors: Kubzansky LD, Bordelois P, Jun HJ, Roberts AL, Cerda M, Bluestone N, Koenen KC
Source: JAMA Psychiatry, 2014 Jan;71(1), p. 44-51.
PMID: 24258147
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Long-term use of multivitamins and risk of colorectal adenoma in women.
Authors: Massa J, Cho E, Orav EJ, Willett WC, Wu K, Giovannucci EL
Source: Br J Cancer, 2014 Jan 7;110(1), p. 249-55.
EPub date: 2013 Nov 12.
PMID: 24220696
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Body mass index, waist circumference, physical activity, and risk of hearing loss in women.
Authors: Curhan SG, Eavey R, Wang M, Stampfer MJ, Curhan GC
Source: Am J Med, 2013 Dec;126(12), p. 1142.e1-8.
EPub date: 2013 Oct 11.
PMID: 24125639
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A genome-wide association study of severe teenage acne in European Americans.
Authors: Zhang M, Qureshi AA, Hunter DJ, Han J
Source: Hum Genet, 2014 Mar;133(3), p. 259-64.
EPub date: 2013 Oct 11.
PMID: 24114350
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