|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|
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.
Identification of a melanoma susceptibility locus and somatic mutation in TET2.
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Source: Carcinogenesis, 2014 Sep;35(9), p. 2097-101.
EPub date: 2014 Jun 30.
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.
Genome-wide interaction study of smoking and bladder cancer risk.
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EPub date: 2014 Mar 24.
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EPub date: 2014 Mar 13.
Analgesic use and patterns of estrogen metabolism in premenopausal women.
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EPub date: 2014 Jan 10.
Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case-control study.
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Genome-wide association study identifies multiple loci associated with bladder cancer risk.
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EPub date: 2013 Oct 24.
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.
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
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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.
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.
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Source: Rheumatol Int, 2014 Mar;34(3), p. 407-11.
EPub date: 2013 Sep 24.
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.
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.
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.
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.
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.
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.