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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

Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses' Health Study II.
Authors: Wang J, Eliassen AH, Spiegelman D, Willett WC, Hankinson SE
Source: Cancer Causes Control, 2014 Jul;25(7), p. 819-27.
EPub date: 2014 Apr 20.
PMID: 24748579
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Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses' Health Study (NHS) and NHSII cohorts.
Authors: Sun Q, Cornelis MC, Townsend MK, Tobias DK, Eliassen AH, Franke AA, Hauser R, Hu FB
Source: Environ Health Perspect, 2014 Jun;122(6), p. 616-23.
EPub date: 2014 Mar 13.
PMID: 24633239
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Analgesic use and patterns of estrogen metabolism in premenopausal women.
Authors: Fortner RT, Oh H, Daugherty SE, Xu X, Hankinson SE, Ziegler RG, Eliassen AH
Source: Horm Cancer, 2014 Apr;5(2), p. 104-12.
EPub date: 2014 Jan 10.
PMID: 24407556
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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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Genome-wide association study identifies multiple loci associated with bladder cancer risk.
Authors: Figueroa JD, Ye Y, Siddiq A, Garcia-Closas M, Chatterjee N, Prokunina-Olsson L, Cortessis VK, Kooperberg C, Cussenot O, Benhamou S, Prescott J, Porru S, Dinney CP, Malats N, Baris D, Purdue M, Jacobs EJ, Albanes D, Wang Z, Deng X, Chung CC, Tang W, Bas Bueno-de-Mesquita H, Trichopoulos D, Ljungberg B, Clavel-Chapelon F, Weiderpass E, Krogh V, Dorronsoro M, Travis R, Tjřnneland A, Brenan P, Chang-Claude J, Riboli E, Conti D, Gago-Dominguez M, Stern MC, Pike MC, Van Den Berg D, Yuan JM, Hohensee C, Rodabough R, Cancel-Tassin G, Roupret M, Comperat E, Chen C, De Vivo I, Giovannucci E, Hunter DJ, Kraft P, Lindstrom S, Carta A, Pavanello S, Arici C, Mastrangelo G, Kamat AM, Lerner SP, Barton Grossman H, Lin J, Gu J, Pu X, Hutchinson A, Burdette L, Wheeler W, Kogevinas M, Tardón A, Serra C, Carrato A, García-Closas R, Lloreta J, Schwenn M, Karagas MR, Johnson A, Schned A, Armenti KR, Hosain GM, Andriole G Jr, Grubb R 3rd, Black A, Ryan Diver W, Gapstur SM, Weinstein SJ, Virtamo J, Haiman CA, Landi MT, Caporaso N, Fraumeni JF Jr, Vineis P, Wu X, Silverman DT, Chanock S, Rothman N
Source: Hum Mol Genet, 2014 Mar 1;23(5), p. 1387-98.
EPub date: 2013 Oct 24.
PMID: 24163127
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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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Plasma C-peptide, mammographic breast density, and risk of invasive breast cancer.
Authors: Ahern TP, Hankinson SE, Willett WC, Pollak MN, Eliassen AH, Tamimi RM
Source: Cancer Epidemiol Biomarkers Prev, 2013 Oct;22(10), p. 1786-96.
PMID: 24097198
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Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.
Authors: Rudolph A, Hein R, Lindström S, Beckmann L, Behrens S, Liu J, Aschard H, Bolla MK, Wang J, Truong T, Cordina-Duverger E, Menegaux F, Brüning T, Harth V, GENICA Network, Severi G, Baglietto L, Southey M, Chanock SJ, Lissowska J, Figueroa JD, Eriksson M, Humpreys K, Darabi H, Olson JE, Stevens KN, Vachon CM, Knight JA, Glendon G, Mulligan AM, Ashworth A, Orr N, Schoemaker M, Webb PM, kConFab Investigators, AOCS Management Group, Guénel P, Brauch H, Giles G, García-Closas M, Czene K, Chenevix-Trench G, Couch FJ, Andrulis IL, Swerdlow A, Hunter DJ, Flesch-Janys D, Easton DF, Hall P, Nevanlinna H, Kraft P, Chang-Claude J, Breast Cancer Association Consortium
Source: Endocr Relat Cancer, 2013 Dec;20(6), p. 875-87.
EPub date: 2013 Nov 4.
PMID: 24080446
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Comparison of the 1987 American College of Rheumatology and the 2010 American College of Rheumatology/European League against Rheumatism criteria for classification of rheumatoid arthritis in the Nurses' Health Study cohorts.
Authors: Kasturi S, Goldstein BL, Malspeis S, Karlson EW, Costenbader KH
Source: Rheumatol Int, 2014 Mar;34(3), p. 407-11.
EPub date: 2013 Sep 24.
PMID: 24061933
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Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses' Health Studies: a prospective cohort study.
Authors: Townsend MK, Franke AA, Li X, Hu FB, Eliassen AH
Source: Environ Health, 2013 Sep 13;12(1), p. 80.
EPub date: 2013 Sep 13.
PMID: 24034517
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A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor ? receptor 2 levels and risk of ovarian cancer.
Authors: Poole EM, Lee IM, Ridker PM, Buring JE, Hankinson SE, Tworoger SS
Source: Am J Epidemiol, 2013 Oct 15;178(8), p. 1256-64.
EPub date: 2013 Aug 21.
PMID: 23966559
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A 20-year prospective study of plasma prolactin as a risk marker of breast cancer development.
Authors: Tworoger SS, Eliassen AH, Zhang X, Qian J, Sluss PM, Rosner BA, Hankinson SE
Source: Cancer Res, 2013 Aug 1;73(15), p. 4810-9.
EPub date: 2013 Jun 19.
PMID: 23783576
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Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies.
Authors: Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL
Source: Medicine (Baltimore), 2013 May;92(3), p. 123-31.
PMID: 23625163
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Analgesic use in relation to sex hormone and prolactin concentrations in premenopausal women.
Authors: Bauer SR, Fortner RT, Gates MA, Eliassen AH, Hankinson SE, Tworoger SS
Source: Cancer Causes Control, 2013 Jun;24(6), p. 1087-97.
EPub date: 2013 Mar 21.
PMID: 23515936
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Premenopausal endogenous steroid hormones and breast cancer risk: results from the Nurses' Health Study II.
Authors: Fortner RT, Eliassen AH, Spiegelman D, Willett WC, Barbieri RL, Hankinson SE
Source: Breast Cancer Res, 2013 Mar 6;15(2), p. R19.
EPub date: 2013 Mar 6.
PMID: 23497468
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Association of environmental and genetic factors and gene-environment interactions with risk of developing rheumatoid arthritis.
Authors: Karlson EW, Ding B, Keenan BT, Liao K, Costenbader KH, Klareskog L, Alfredsson L, Chibnik LB
Source: Arthritis Care Res (Hoboken), 2013 Jul;65(7), p. 1147-56.
PMID: 23495093
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A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication.
Authors: Hein R, Flesch-Janys D, Dahmen N, Beckmann L, Lindström S, Schoof N, Czene K, Mittelstraß K, Illig T, Seibold P, Behrens S, Humphreys K, Li J, Liu J, Olson JE, Wang X, Hankinson SE, Truong T, Menegaux F, Dos Santos Silva I, Johnson N, GENICA Network, Chen ST, Yu JC, Ziogas A, Kataja V, Kosma VM, Mannermaa A, Anton-Culver H, Shen CY, Brauch H, Peto J, Guénel P, Kraft P, Couch FJ, Easton DF, Hall P, Chang-Claude J
Source: Breast Cancer Res Treat, 2013 Apr;138(2), p. 529-42.
EPub date: 2013 Feb 20.
PMID: 23423446
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