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Grant Details

Grant Number: 5U01CA067262-06 Interpret this number
Primary Investigator: Willett, Walter
Organization: Harvard University (Sch Of Public Hlth)
Project Title: Premenopausal Hormone Levels and Risk of Breast Cancer
Fiscal Year: 2001
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Abstract

The epidemiology of breast cancer suggests a central etiologic role for premenopausal endogenous sex hormones, yet current data do not indicate which specific endogenous hormones (or hormone fractions) are of greatest importance and at what levels risk is increased. Similarly, current data suggest that urinary estrogen metabolites and plasma antioxidants may also be related to breast cancer risk yet these relations have not been assessed in a large prospective study. The Nurses' Health Study Il (NHSII) is a large ongoing prospective cohort study of 116,678 female, U.S. registered nurses who were 25-42 years Of age when the study began in 1989. We now propose to collect and archive blood and urine samples from approximately 40,000 premenopausal women participating in the NHSII who are at least 35 years of age, are free from cancer, have completed previous NHSII questionnaires, are not using exogenous hormones and are neither pregnant nor breastfeeding. Plasma drawn during both the follicular phase (days 3-5) and luteal phase (approx days 20-22), white and red blood cells, and a urine sample will be stored in liquid nitrogen freezers and later analyzed using a nested case-control design. We propose to assess the following specific hypotheses: (1) higher levels of estrogens, androgens, prolactin and progesterone in both the follicular and luteal phase of the menstrual cycle each increase risk of breast cancer, (2) higher levels of plasma beta-carotene and other carotenoids, retinol, and alpha-tocopherol reduce the risk of breast cancer and (3) the ratio of 16-alpha to 2-hydroxylated urinary metabolites is positively associated with an increased risk of breast cancer. The ongoing NHSII will provide follow-up of the cohort and documentation of breast cancer (CA 50385) in addition to information on important covariates (such as body mass index, parity, age at menarche, smoking status and dietary intake, among others) for the proposed study. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed covariate data, and the ability to collect blood specimens timed according to the menstrual cycle provide a unique opportunity to evaluate several important hypotheses related to breast cancer risk.

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Publications

The association of body size in early to mid-life with adult urinary 6-sulfatoxymelatonin levels among night shift health care workers.
Authors: Ramin CA, Massa J, Wegrzyn LR, Brown SB, Pierre-Paul J, Devore EE, Hankinson SE, Schernhammer ES
Source: BMC Public Health, 2015 May 6;15, p. 467.
EPub date: 2015 May 6.
PMID: 25943349
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Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses' health studies.
Authors: Sisti JS, Lindström S, Kraft P, Tamimi RM, Rosner BA, Wu T, Willett WC, Eliassen AH
Source: Breast Cancer Res Treat, 2015 Jun;151(2), p. 415-25.
EPub date: 2015 Apr 28.
PMID: 25917867
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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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Endogenous levels of circulating androgens and risk of Crohn's disease and ulcerative colitis among women: a nested case-control study from the nurses' health study cohorts.
Authors: Khalili H, Ananthakrishnan AN, Konijeti GG, Higuchi LM, Fuchs CS, Richter JM, Tworoger SS, Hankinson SE, Chan AT
Source: Inflamm Bowel Dis, 2015 Jun;21(6), p. 1378-85.
PMID: 25844961
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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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Teenage acne and cancer risk in US women: A prospective cohort study.
Authors: Zhang M, Qureshi AA, Fortner RT, Hankinson SE, Wei Q, Wang LE, Eliassen AH, Willett WC, Hunter DJ, Han J
Source: Cancer, 2015 May 15;121(10), p. 1681-7.
EPub date: 2015 Jan 8.
PMID: 25572604
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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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Migraine and breast cancer risk: a prospective cohort study and meta-analysis.
Authors: Winter AC, Rice MS, Fortner RT, Eliassen AH, Kurth T, Tamimi RM
Source: J Natl Cancer Inst, 2015 Jan;107(1), p. 381.
EPub date: 2014 Dec 12.
PMID: 25505231
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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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MicroRNA related polymorphisms and breast cancer risk.
Authors: Khan S, Greco D, Michailidou K, Milne RL, Muranen TA, Heikkinen T, Aaltonen K, Dennis J, Bolla MK, Liu J, Hall P, Irwanto A, Humphreys K, Li J, Czene K, Chang-Claude J, Hein R, Rudolph A, Seibold P, Flesch-Janys D, Fletcher O, Peto J, dos Santos Silva I, Johnson N, Gibson L, Aitken Z, Hopper JL, Tsimiklis H, Bui M, Makalic E, Schmidt DF, Southey MC, Apicella C, Stone J, Waisfisz Q, Meijers-Heijboer H, Adank MA, van der Luijt RB, Meindl A, Schmutzler RK, Müller-Myhsok B, Lichtner P, Turnbull C, Rahman N, Chanock SJ, Hunter DJ, Cox A, Cross SS, Reed MW, Schmidt MK, Broeks A, Van't Veer LJ, Hogervorst FB, Fasching PA, Schrauder MG, Ekici AB, Beckmann MW, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Benitez J, Zamora PM, Perez JI, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Pharoah PD, Dunning AM, Shah M, Luben R, Brown J, Couch FJ, Wang X, Vachon C, Olson JE, Lambrechts D, Moisse M, Paridaens R, Christiaens MR, Guénel P, Truong T, Laurent-Puig P, Mulot C, Marme F, Burwinkel B, Schneeweiss A, Sohn C, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Andrulis IL, Knight JA, Tchatchou S, Mulligan AM, Dörk T, Bogdanova NV, Antonenkova NN, Anton-Culver H, Darabi H, Eriksson M, Garcia-Closas M, Figueroa J, Lissowska J, Brinton L, Devilee P, Tollenaar RA, Seynaeve C, van Asperen CJ, Kristensen VN, kConFab Investigators, Australian Ovarian Cancer Study Group, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Lindblom A, Margolin S, Radice P, Peterlongo P, Barile M, Mariani P, Hooning MJ, Martens JW, Collée JM, Jager A, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Giles GG, McLean C, Brauch H, Brüning T, Ko YD, GENICA Network, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Swerdlow A, Ashworth A, Orr N, Jones M, Simard J, Goldberg MS, Labrèche F, Dumont M, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Kataja V, Kosma VM, Hartikainen JM, Mannermaa A, Hamann U, Chenevix-Trench G, Blomqvist C, Aittomäki K, Easton DF, Nevanlinna H
Source: PLoS One, 2014;9(11), p. e109973.
EPub date: 2014 Nov 12.
PMID: 25390939
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The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.
Authors: Fu YP, Kohaar I, Moore LE, Lenz P, Figueroa JD, Tang W, Porter-Gill P, Chatterjee N, Scott-Johnson A, Garcia-Closas M, Muchmore B, Baris D, Paquin A, Ylaya K, Schwenn M, Apolo AB, Karagas MR, Tarway M, Johnson A, Mumy A, Schned A, Guedez L, Jones MA, Kida M, Hosain GM, Malats N, Kogevinas M, Tardon A, Serra C, Carrato A, Garcia-Closas R, Lloreta J, Wu X, Purdue M, Andriole GL Jr, Grubb RL 3rd, Black A, Landi MT, Caporaso NE, Vineis P, Siddiq A, Bueno-de-Mesquita HB, Trichopoulos D, Ljungberg B, Severi G, Weiderpass E, Krogh V, Dorronsoro M, Travis RC, Tjønneland A, Brennan P, Chang-Claude J, Riboli E, Prescott J, Chen C, De Vivo I, Govannucci E, Hunter D, Kraft P, Lindstrom S, Gapstur SM, Jacobs EJ, Diver WR, Albanes D, Weinstein SJ, Virtamo J, Kooperberg C, Hohensee C, Rodabough RJ, Cortessis VK, Conti DV, Gago-Dominguez M, Stern MC, Pike MC, Van Den Berg D, Yuan JM, Haiman CA, Cussenot O, Cancel-Tassin G, Roupret M, Comperat E, Porru S, Carta A, Pavanello S, Arici C, Mastrangelo G, Grossman HB, Wang Z, Deng X, Chung CC, Hutchinson A, Burdette L, Wheeler W, Fraumeni J Jr, Chanock SJ, Hewitt SM, Silverman DT, Rothman N, Prokunina-Olsson L
Source: Cancer Res, 2014 Oct 15;74(20), p. 5808-18.
PMID: 25320178
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Bioactive prolactin levels and risk of breast cancer: a nested case-control study.
Authors: Tworoger SS, Rice MS, Rosner BA, Feeney YB, Clevenger CV, Hankinson SE
Source: Cancer Epidemiol Biomarkers Prev, 2015 Jan;24(1), p. 73-80.
EPub date: 2014 Oct 14.
PMID: 25315962
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