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Grant Details

Grant Number: 5R01CA074847-03 Interpret this number
Primary Investigator: Ursin, Giske
Organization: University Of Southern California
Project Title: BRCA1, Oral Contraceptives, and Hormonal Risk Factors
Fiscal Year: 2001
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Abstract

Mutations in the breast cancer susceptibility gene BRCA1 may be involved in a substantial number of breast cancer diagnosed at an early age. However, the age at which breast cancer occurs appears to vary substantially, even in women from the same family with the same mutation. Further recent evidence suggests that breast cancer risk in BRCA1 mutation carriers is much lower than the previously reported 85%. This suggests that other, genetic or non-genetic, factors play a role in whether or when breast cancer occurs in women with a BRCA1 mutation. Epidemiological evidence suggests that oral contraceptive (OC) use at an early age may increase risk of breast cancer. Further, OC use appears to be particularly. Detrimental in young women with a family history. We have preliminary data suggesting that BRCA1 mutation carriers have a much higher risk associated with OC use than non- carriers. Such a detrimental effect of OC use in BRCA1 mutation carriers could be due to increased breast cell proliferation in these women. Experimental evidence suggests that BRCA1 may be a hormonally induced negative growth regulator. We propose to conduct a population-based study to determine the ration of relative risk of breast cancer associated with OC use in BRCA1 mutation carriers and the relative risk of breast cancer associated with OC use in non-carriers. This information can subsequently be used to determine the relative risk of breast cancer associated with OC use in BRCA1 mutation carriers. The secondary aims of this study are to determine whether other hormonal risk factors such as selected reproductive factors and physical exercise differentially affects breast cancer risk in BRCA1 mutation carriers and non-carriers, to determine whether BRCA1 mutation carriers have different mammographic density profiles that on carriers, and to determine whether mammographic densities are affected by OC use differentially in BRCA1 mutation carriers than non-carriers. This study will provide valuable epidemiologic information regarding the role of BRCA1 in breast cancer etiology, and could yield important results in developing intervention regimens and appropriate counseling for women with a BRCA1 mutation.

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Publications

Estimating risks for variants of unknown significance according to their predicted pathogenicity classes with application to BRCA1.
Authors: Dowty JG, Lee E, McKean-Cowdin R, Henderson BE, Bernstein L, Ursin G, Hopper JL
Source: Breast Cancer Res Treat, 2014 Feb;144(1), p. 171-7.
EPub date: 2014 Jan 31.
PMID: 24481681
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Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk.
Authors: Vachon CM, Scott CG, Fasching PA, Hall P, Tamimi RM, Li J, Stone J, Apicella C, Odefrey F, Gierach GL, Jud SM, Heusinger K, Beckmann MW, Pollan M, Fernández-Navarro P, Gonzalez-Neira A, Benitez J, van Gils CH, Lokate M, Onland-Moret NC, Peeters PH, Brown J, Leyland J, Varghese JS, Easton DF, Thompson DJ, Luben RN, Warren RM, Wareham NJ, Loos RJ, Khaw KT, Ursin G, Lee E, Gayther SA, Ramus SJ, Eeles RA, Leach MO, Kwan-Lim G, Couch FJ, Giles GG, Baglietto L, Krishnan K, Southey MC, Le Marchand L, Kolonel LN, Woolcott C, Maskarinec G, Haiman CA, Walker K, Johnson N, McCormack VA, Biong M, Alnaes GI, Gram IT, Kristensen VN, Břrresen-Dale AL, Lindström S, Hankinson SE, Hunter DJ, Andrulis IL, Knight JA, Boyd NF, Figuero JD, Lissowska J, Wesolowska E, Peplonska B, Bukowska A, Reszka E, Liu J, Eriksson L, Czene K, Audley T, Wu AH, Pankratz VS, Hopper JL, dos-Santos-Silva I
Source: Cancer Epidemiol Biomarkers Prev, 2012 Jul;21(7), p. 1156-66.
EPub date: 2012 Mar 27.
PMID: 22454379
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Characteristics of triple-negative breast cancer in patients with a BRCA1 mutation: results from a population-based study of young women.
Authors: Lee E, McKean-Cowdin R, Ma H, Spicer DV, Van Den Berg D, Bernstein L, Ursin G
Source: J Clin Oncol, 2011 Nov 20;29(33), p. 4373-80.
EPub date: 2011 Oct 17.
PMID: 22010008
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Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study.
Authors: Lee E, Ma H, McKean-Cowdin R, Van Den Berg D, Bernstein L, Henderson BE, Ursin G
Source: Cancer Epidemiol Biomarkers Prev, 2008 Nov;17(11), p. 3170-8.
PMID: 18990759
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Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients.
Authors: Lee E, McKean-Cowdin R, Ma H, Chen Z, Van Den Berg D, Henderson BE, Bernstein L, Ursin G
Source: Breast Cancer Res, 2008;10(1), p. R19.
EPub date: 2008 Feb 19.
PMID: 18284688
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Mitochondrial DNA G10398A variant is not associated with breast cancer in African-American women.
Authors: Setiawan VW, Chu LH, John EM, Ding YC, Ingles SA, Bernstein L, Press MF, Ursin G, Haiman CA, Neuhausen SL
Source: Cancer Genet Cytogenet, 2008 Feb;181(1), p. 16-9.
PMID: 18262047
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Low-dose medical radiation exposure and breast cancer risk in women under age 50 years overall and by estrogen and progesterone receptor status: results from a case-control and a case-case comparison.
Authors: Ma H, Hill CK, Bernstein L, Ursin G
Source: Breast Cancer Res Treat, 2008 May;109(1), p. 77-90.
EPub date: 2007 Jul 7.
PMID: 17616809
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Cigarette smoking is not associated with breast cancer risk in young women.
Authors: Prescott J, Ma H, Bernstein L, Ursin G
Source: Cancer Epidemiol Biomarkers Prev, 2007 Mar;16(3), p. 620-2.
PMID: 17372262
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Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case-control and a case-case comparison.
Authors: Ma H, Bernstein L, Ross RK, Ursin G
Source: Breast Cancer Res, 2006;8(4), p. R39.
PMID: 16846528
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