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Grant Details

Grant Number: 7U01CA083178-06 Interpret this number
Primary Investigator: Bernstein, Jonine
Organization: Sloan-Kettering Inst Can Res
Project Title: Breast Cancer, Radiation Exposure, and the Atm Gene
Fiscal Year: 2003
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Abstract

The objective of this study is to investigate gene-environment interactions in the etiology of breast cancer. We propose to establish a repository of epidemiologic risk factor information and biologic specimens from 900 women with asynchronous bilateral breast cancer and 2700 women with unilateral breast cancer who will be ascertained through 6 population-based tumor registries in the US and Denmark. All subjects will be interviewed using a structured questionnaire and blood samples will be collected for genetic analyses. Our initial plan for using this repository is to examine the interaction of radiation exposure, the ATM gene, and breast cancer. Ionizing radiation is known to be a breast carcinogen and recent studies suggest that the ATM gene may increase susceptibility to radiation-induced breast cancer. Our hypothesis is that women who are ATM gene carriers and who have received radiation therapy as part of breast conservation treatment, are at especially high risk of developing second primary contralateral breast cancer. We will also provide descriptive statistics on the prevalence of ATM in this large population-based sample of women. ATM heterozygosity will be assessed through an efficient staged approach appropriate for analysis of this complex gene. For subjects who received RT, radiation scatter dose to the contralateral breast will be reconstructed. The unique repository that we establish will be critical for future interdisciplinary investigations into the mechanisms and nature of gene-gene and gene-environment interaction influencing susceptibility to breast cancer. The study of second primaries presents a particularly promising context in which to disentangle the complex interactions among hormonal, genetic, and environmental factors influencing breast carcinogenesis as any important etiologic factors (e.g. genetic abnormalities) will be more prevalent among women who already have breast cancer than in the general population. Further, the rising incidence of breast cancer coupled with improved survival, has placed an increased number of women at risk for second primary breast cancer making it an issue of public health importance.

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Publications

Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study.
Authors: Figueiredo JC, Haile RW, Bernstein L, Malone KE, Largent J, Langholz B, Lynch CF, Bertelsen L, Capanu M, Concannon P, Borg A, Børresen-Dale AL, Diep A, Teraoka S, Torngren T, Xue S, Bernstein JL
Source: Breast Cancer Res Treat, 2010 Feb;120(1), p. 175-83.
EPub date: 2009 Jul 14.
PMID: 19597986
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Alcohol intake and cigarette smoking and risk of a contralateral breast cancer: The Women's Environmental Cancer and Radiation Epidemiology Study.
Authors: Knight JA, Bernstein L, Largent J, Capanu M, Begg CB, Mellemkjaer L, Lynch CF, Malone KE, Reiner AS, Liang X, Haile RW, Boice JD Jr, WECARE Study Collaborative Group, Bernstein JL
Source: Am J Epidemiol, 2009 Apr 15;169(8), p. 962-8.
EPub date: 2009 Feb 11.
PMID: 19211621
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Variants in the ATM gene associated with a reduced risk of contralateral breast cancer.
Authors: Concannon P, Haile RW, Børresen-Dale AL, Rosenstein BS, Gatti RA, Teraoka SN, Diep TA, Jansen L, Atencio DP, Langholz B, Capanu M, Liang X, Begg CB, Thomas DC, Bernstein L, Olsen JH, Malone KE, Lynch CF, Anton-Culver H, Bernstein JL, Women's Environment, Cancer, and Radiation Epidemiology Study Collaborative Group
Source: Cancer Res, 2008 Aug 15;68(16), p. 6486-91.
PMID: 18701470
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Dose to the contralateral breast from radiotherapy and risk of second primary breast cancer in the WECARE study.
Authors: Stovall M, Smith SA, Langholz BM, Boice JD Jr, Shore RE, Andersson M, Buchholz TA, Capanu M, Bernstein L, Lynch CF, Malone KE, Anton-Culver H, Haile RW, Rosenstein BS, Reiner AS, Thomas DC, Bernstein JL, Women's Environmental, Cancer, and Radiation Epidemiology Study Collaborative Group
Source: Int J Radiat Oncol Biol Phys, 2008 Nov 15;72(4), p. 1021-30.
EPub date: 2008 Jun 14.
PMID: 18556141
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Oral contraceptives, postmenopausal hormones, and risk of asynchronous bilateral breast cancer: the WECARE Study Group.
Authors: Figueiredo JC, Bernstein L, Capanu M, Malone KE, Lynch CF, Anton-Culver H, Stovall M, Bertelsen L, Haile RW, Bernstein JL, WECARE Study Group
Source: J Clin Oncol, 2008 Mar 20;26(9), p. 1411-8.
EPub date: 2008 Feb 4.
PMID: 18250348
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Study design: evaluating gene-environment interactions in the etiology of breast cancer - the WECARE study.
Authors: Bernstein JL, Langholz B, Haile RW, Bernstein L, Thomas DC, Stovall M, Malone KE, Lynch CF, Olsen JH, Anton-Culver H, Shore RE, Boice JD Jr, Berkowitz GS, Gatti RA, Teitelbaum SL, Smith SA, Rosenstein BS, Børresen-Dale AL, Concannon P, Thompson WD, WECARE study
Source: Breast Cancer Res, 2004;6(3), p. R199-214.
EPub date: 2004 Mar 9.
PMID: 15084244
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ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer.
Authors: Bernstein JL, Bernstein L, Thompson WD, Lynch CF, Malone KE, Teitelbaum SL, Olsen JH, Anton-Culver H, Boice JD, Rosenstein BS, Børresen-Dale AL, Gatti RA, Concannon P, Haile RW, WECARE Study Collaborative Group
Source: Br J Cancer, 2003 Oct 20;89(8), p. 1513-6.
PMID: 14562025
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Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with breast cancer.
Authors: Bernstein JL, Teraoka S, Haile RW, Børresen-Dale AL, Rosenstein BS, Gatti RA, Diep AT, Jansen L, Atencio DP, Olsen JH, Bernstein L, Teitelbaum SL, Thompson WD, Concannon P, WECARE Study Collaborative Group
Source: Hum Mutat, 2003 May;21(5), p. 542-50.
PMID: 12673797
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