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Grant Details

Grant Number: 5R01CA050385-24 Interpret this number
Primary Investigator: Willett, Walter
Organization: Harvard School Of Public Health
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

Alcohol Intake and Risk of Incident Psoriatic Arthritis in Women.
Authors: Wu S, Cho E, Li WQ, Han J, Qureshi AA
Source: J Rheumatol, 2015 Apr 1;null, p. null.
EPub date: 2015 Apr 1.
PMID: 25834201
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Investigation of dietary factors and endometrial cancer risk using a nutrient-wide association study approach in the EPIC and Nurses' Health Study (NHS) and NHSII.
Authors: Merritt MA, Tzoulaki I, Tworoger SS, De Vivo I, Hankinson SE, Fernandes J, Tsilidis KK, Weiderpass E, Tjønneland A, Petersen KE, Dahm CC, Overvad K, Dossus L, Boutron-Ruault MC, Fagherazzi G, Fortner RT, Kaaks R, Aleksandrova K, Boeing H, Trichopoulou A, Bamia C, Trichopoulos D, Palli D, Grioni S, Tumino R, Sacerdote C, Mattiello A, Bueno-de-Mesquita HB, Onland-Moret NC, Peeters PH, Gram IT, Skeie G, Quirós JR, Duell EJ, Sánchez MJ, Salmerón D, Barricarte A, Chamosa S, Ericson U, Sonestedt E, Nilsson LM, Idahl A, Khaw KT, Wareham N, Travis RC, Rinaldi S, Romieu I, Patel CJ, Riboli E, Gunter MJ
Source: Cancer Epidemiol Biomarkers Prev, 2015 Feb;24(2), p. 466-71.
PMID: 25662427
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Urinary melatonin concentration and the risk of breast cancer in Nurses' Health Study II.
Authors: Brown SB, Hankinson SE, Eliassen AH, Reeves KW, Qian J, Arcaro KF, Wegrzyn LR, Willett WC, Schernhammer ES
Source: Am J Epidemiol, 2015 Feb 1;181(3), p. 155-62.
EPub date: 2015 Jan 13.
PMID: 25587174
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Total and cause-specific mortality of U.S. nurses working rotating night shifts.
Authors: Gu F, Han J, Laden F, Pan A, Caporaso NE, Stampfer MJ, Kawachi I, Rexrode KM, Willett WC, Hankinson SE, Speizer FE, Schernhammer ES
Source: Am J Prev Med, 2015 Mar;48(3), p. 241-52.
EPub date: 2015 Jan 6.
PMID: 25576495
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Posttraumatic stress disorder and incidence of type 2 diabetes mellitus in a sample of women: a 22-year longitudinal study.
Authors: Roberts AL, Agnew-Blais JC, Spiegelman D, Kubzansky LD, Mason SM, Galea S, Hu FB, Rich-Edwards JW, Koenen KC
Source: JAMA Psychiatry, 2015 Mar;72(3), p. 203-10.
PMID: 25565410
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Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer.
Authors: Bertrand KA, Rosner B, Eliassen AH, Hankinson SE, Rexrode KM, Willett W, Tamimi RM
Source: Breast Cancer Res Treat, 2015 Jan;149(2), p. 479-87.
EPub date: 2014 Dec 28.
PMID: 25543181
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Rice consumption and risk of cardiovascular disease: results from a pooled analysis of 3 U.S. cohorts.
Authors: Muraki I, Wu H, Imamura F, Laden F, Rimm EB, Hu FB, Willett WC, Sun Q
Source: Am J Clin Nutr, 2015 Jan;101(1), p. 164-72.
EPub date: 2014 Nov 12.
PMID: 25527760
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Immunoassay and Nb2 lymphoma bioassay prolactin levels and mammographic density in premenopausal and postmenopausal women the Nurses' Health Studies.
Authors: Rice MS, Tworoger SS, Bertrand KA, Hankinson SE, Rosner BA, Feeney YB, Clevenger CV, Tamimi RM
Source: Breast Cancer Res Treat, 2015 Jan;149(1), p. 245-53.
EPub date: 2014 Dec 13.
PMID: 25503962
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