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Grant Details

Grant Number: 5R01CA050385-25 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: 2013
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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.

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Publications

Urinary Excretion of Select Dietary Polyphenol Metabolites Is Associated with a Lower Risk of Type 2 Diabetes in Proximate but Not Remote Follow-Up in a Prospective Investigation in 2 Cohorts of US Women.
Authors: Sun Q, Wedick NM, Tworoger SS, Pan A, Townsend MK, Cassidy A, Franke AA, Rimm EB, Hu FB, van Dam RM
Source: J Nutr, 2015 Jun;145(6), p. 1280-8.
EPub date: 2015 Apr 22.
PMID: 25904735
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Long-term risk of type 2 diabetes mellitus in relation to BMI and weight change among women with a history of gestational diabetes mellitus: a prospective cohort study.
Authors: Bao W, Yeung E, Tobias DK, Hu FB, Vaag AA, Chavarro JE, Mills JL, Grunnet LG, Bowers K, Ley SH, Kiely M, Olsen SF, Zhang C
Source: Diabetologia, 2015 Jun;58(6), p. 1212-9.
EPub date: 2015 Mar 22.
PMID: 25796371
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Sleep disordered breathing and the risk of psoriasis among US women.
Authors: Cohen JM, Jackson CL, Li TY, Wu S, Qureshi AA
Source: Arch Dermatol Res, 2015 Jul;307(5), p. 433-8.
EPub date: 2015 Feb 13.
PMID: 25676527
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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, Tjřnneland 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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Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.
Authors: Debette S, Ibrahim Verbaas CA, Bressler J, Schuur M, Smith A, Bis JC, Davies G, Wolf C, Gudnason V, Chibnik LB, Yang Q, deStefano AL, de Quervain DJ, Srikanth V, Lahti J, Grabe HJ, Smith JA, Priebe L, Yu L, Karbalai N, Hayward C, Wilson JF, Campbell H, Petrovic K, Fornage M, Chauhan G, Yeo R, Boxall R, Becker J, Stegle O, Mather KA, Chouraki V, Sun Q, Rose LM, Resnick S, Oldmeadow C, Kirin M, Wright AF, Jonsdottir MK, Au R, Becker A, Amin N, Nalls MA, Turner ST, Kardia SL, Oostra B, Windham G, Coker LH, Zhao W, Knopman DS, Heiss G, Griswold ME, Gottesman RF, Vitart V, Hastie ND, Zgaga L, Rudan I, Polasek O, Holliday EG, Schofield P, Choi SH, Tanaka T, An Y, Perry RT, Kennedy RE, Sale MM, Wang J, Wadley VG, Liewald DC, Ridker PM, Gow AJ, Pattie A, Starr JM, Porteous D, Liu X, Thomson R, Armstrong NJ, Eiriksdottir G, Assareh AA, Kochan NA, Widen E, Palotie A, Hsieh YC, Eriksson JG, Vogler C, van Swieten JC, Shulman JM, Beiser A, Rotter J, Schmidt CO, Hoffmann W, Nöthen MM, Ferrucci L, Attia J, Uitterlinden AG, Amouyel P, Dartigues JF, Amieva H, Räikkönen K, Garcia M, Wolf PA, Hofman A, Longstreth WT Jr, Psaty BM, Boerwinkle E, DeJager PL, Sachdev PS, Schmidt R, Breteler MM, Teumer A, Lopez OL, Cichon S, Chasman DI, Grodstein F, Müller-Myhsok B, Tzourio C, Papassotiropoulos A, Bennett DA, Ikram MA, Deary IJ, van Duijn CM, Launer L, Fitzpatrick AL, Seshadri S, Mosley TH Jr, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
Source: Biol Psychiatry, 2015 Apr 15;77(8), p. 749-63.
EPub date: 2014 Nov 25.
PMID: 25648963
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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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