Skip Navigation
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
Back to top


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.

Back to top


Publications

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
Related Citations

Back to top


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
Related Citations

Back to top


Genome-wide interaction study of smoking and bladder cancer risk.
Authors: Figueroa JD, Han SS, Garcia-Closas M, Baris D, Jacobs EJ, Kogevinas M, Schwenn M, Malats N, Johnson A, Purdue MP, Caporaso N, Landi MT, Prokunina-Olsson L, Wang Z, Hutchinson A, Burdette L, Wheeler W, Vineis P, Siddiq A, Cortessis VK, Kooperberg C, Cussenot O, Benhamou S, Prescott J, Porru S, Bueno-de-Mesquita HB, 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, Karagas MR, Schned A, Armenti KR, Hosain GM, Haiman CA, Fraumeni JF Jr, Chanock SJ, Chatterjee N, Rothman N, Silverman DT
Source: Carcinogenesis, 2014 Aug;35(8), p. 1737-44.
EPub date: 2014 Mar 24.
PMID: 24662972
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations

Back to top


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
Related Citations