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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

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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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, Labrčche 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, Tjřnneland 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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Alcohol consumption in relation to plasma sex hormones, prolactin, and sex hormone-binding globulin in premenopausal women.
Authors: Hirko KA, Spiegelman D, Willett WC, Hankinson SE, Eliassen AH
Source: Cancer Epidemiol Biomarkers Prev, 2014 Dec;23(12), p. 2943-53.
EPub date: 2014 Oct 3.
PMID: 25281368
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Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.
Authors: Lin WY, Camp NJ, Ghoussaini M, Beesley J, Michailidou K, Hopper JL, Apicella C, Southey MC, Stone J, Schmidt MK, Broeks A, Van't Veer LJ, Th Rutgers EJ, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Bolla MK, Wang Q, Dennis J, Sawyer EJ, Cheng T, Tomlinson I, Kerin MJ, Miller N, Marmé F, Surowy HM, Burwinkel B, Guénel P, Truong T, Menegaux F, Mulot C, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Benitez J, Zamora MP, Arias Perez JI, Menéndez P, González-Neira A, Pita G, Alonso MR, Alvarez N, Herrero D, Anton-Culver H, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Müller-Myhsok B, Brauch H, Brüning T, Ko YD, GENICA Network, Tessier DC, Vincent D, Bacot F, Nevanlinna H, Aittomäki K, Blomqvist C, Khan S, Matsuo K, Ito H, Iwata H, Horio A, Bogdanova NV, Antonenkova NN, Dörk T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, kConFab Investigators, Australian Ovarian Cancer Study Group, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Neven P, Wauters E, Wildiers H, Lambrechts D, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Radice P, Peterlongo P, Manoukian S, Bonanni B, Couch FJ, Wang X, Vachon C, Purrington K, Giles GG, Milne RL, Mclean C, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labrčche F, Dumont M, Teo SH, Yip CH, Hassan N, Vithana EN, Kristensen V, Zheng W, Deming-Halverson S, Shrubsole MJ, Long J, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Devilee P, Tollenaar RA, Seynaeve C, Van Asperen CJ, García-Closas M, Figueroa J, Lissowska J, Brinton L, Czene K, Darabi H, Eriksson M, Brand JS, Hooning MJ, Hollestelle A, Van Den Ouweland AM, Jager A, Li J, Liu J, Humphreys K, Shu XO, Lu W, Gao YT, Cai H, Cross SS, Reed MW, Blot W, Signorello LB, Cai Q, Pharoah PD, Perkins B, Shah M, Blows FM, Kang D, Yoo KY, Noh DY, Hartman M, Miao H, Chia KS, Putti TC, Hamann U, Luccarini C, Baynes C, Ahmed S, Maranian M, Healey CS, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Sangrajrang S, Gaborieau V, Brennan P, Mckay J, Slager S, Toland AE, Yannoukakos D, Shen CY, Hsiung CN, Wu PE, Ding SL, Ashworth A, Jones M, Orr N, Swerdlow AJ, Tsimiklis H, Makalic E, Schmidt DF, Bui QM, Chanock SJ, Hunter DJ, Hein R, Dahmen N, Beckmann L, Aaltonen K, Muranen TA, Heikkinen T, Irwanto A, Rahman N, Turnbull CA, Breast and Ovarian Cancer Susceptibility (BOCS) Study, Waisfisz Q, Meijers-Heijboer HE, Adank MA, Van Der Luijt RB, Hall P, Chenevix-Trench G, Dunning A, Easton DF, Cox A
Source: Hum Mol Genet, 2015 Jan 1;24(1), p. 285-98.
EPub date: 2014 Aug 28.
PMID: 25168388
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Circulating 25-hydroxyvitamin D level and risk of developing rheumatoid arthritis.
Authors: Hiraki LT, Arkema EV, Cui J, Malspeis S, Costenbader KH, Karlson EW
Source: Rheumatology (Oxford), 2014 Dec;53(12), p. 2243-8.
EPub date: 2014 Jul 26.
PMID: 25065001
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Identification of a melanoma susceptibility locus and somatic mutation in TET2.
Authors: Song F, Amos CI, Lee JE, Lian CG, Fang S, Liu H, MacGregor S, Iles MM, Law MH, Lindeman NI, Montgomery GW, Duffy DL, Cust AE, Jenkins MA, Whiteman DC, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Brown KM, Martin NG, Mann GJ, Bishop DT, Bishop JA, GenoMEL consortium, Kraft P, Qureshi AA, Kanetsky PA, Hayward NK, Hunter DJ, Wei Q, Han J
Source: Carcinogenesis, 2014 Sep;35(9), p. 2097-101.
EPub date: 2014 Jun 30.
PMID: 24980573
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Rationale, design, and method of the Diabetes & Women's Health study--a study of long-term health implications of glucose intolerance in pregnancy and their determinants.
Authors: Zhang C, Hu FB, Olsen SF, Vaag A, Gore-Langton R, Chavarro JE, Bao W, Yeung E, Bowers K, Grunnet LG, Sherman S, Kiely M, Strřm M, Hansen S, Liu A, Mills J, Fan R, DWH study team
Source: Acta Obstet Gynecol Scand, 2014 Nov;93(11), p. 1123-30.
EPub date: 2014 Jun 9.
PMID: 24828694
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