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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
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

Designing And Implementing Quality Control For Multi-center Screening Of Mutations In The Atm Gene Among Women With Breast Cancer
Authors: Bernstein J.L. , Teraoka S. , Haile R.W. , Børresen-Dale A.L. , Rosenstein B.S. , Gatti R.A. , Diep A.T. , Jansen L. , Atencio D.P. , Olsen J.H. , et al. .
Source: Human Mutation, 2003 May; 21(5), p. 542-50.
PMID: 12673797
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Atm Variants 7271t>g And Ivs10-6t>g Among Women With Unilateral And Bilateral Breast Cancer
Authors: Bernstein J.L. , Bernstein L. , Thompson W.D. , Lynch C.F. , Malone K.E. , Teitelbaum S.L. , Olsen J.H. , Anton-Culver H. , Boice J.D. , Rosenstein B.S. , et al. .
Source: British Journal Of Cancer, 2003-10-20 00:00:00.0; 89(8), p. 1513-6.
PMID: 14562025
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Study Design: Evaluating Gene-environment Interactions In The Etiology Of Breast Cancer - The Wecare Study
Authors: Bernstein J.L. , Langholz B. , Haile R.W. , Bernstein L. , Thomas D.C. , Stovall M. , Malone K.E. , Lynch C.F. , Olsen J.H. , Anton-Culver H. , et al. .
Source: Breast Cancer Research : Bcr, 2004; 6(3), p. R199-214.
PMID: 15084244
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Oral Contraceptives, Postmenopausal Hormones, And Risk Of Asynchronous Bilateral Breast Cancer: The Wecare Study Group
Authors: Figueiredo J.C. , Bernstein L. , Capanu M. , Malone K.E. , Lynch C.F. , Anton-Culver H. , Stovall M. , Bertelsen L. , Haile R.W. , Bernstein J.L. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2008-03-20 00:00:00.0; 26(9), p. 1411-8.
PMID: 18250348
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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 S.A. , Langholz B.M. , Boice J.D. , Shore R.E. , Andersson M. , Buchholz T.A. , Capanu M. , Bernstein L. , Lynch C.F. , et al. .
Source: International Journal Of Radiation Oncology, Biology, Physics, 2008-11-15 00:00:00.0; 72(4), p. 1021-30.
PMID: 18556141
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Variants In The Atm Gene Associated With A Reduced Risk Of Contralateral Breast Cancer
Authors: Concannon P. , Haile R.W. , Børresen-Dale A.L. , Rosenstein B.S. , Gatti R.A. , Teraoka S.N. , Diep T.A. , Jansen L. , Atencio D.P. , Langholz B. , et al. .
Source: Cancer Research, 2008-08-15 00:00:00.0; 68(16), p. 6486-91.
PMID: 18701470
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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 J.A. , Bernstein L. , Largent J. , Capanu M. , Begg C.B. , Mellemkjaer L. , Lynch C.F. , Malone K.E. , Reiner A.S. , Liang X. , et al. .
Source: American Journal Of Epidemiology, 2009-04-15 00:00:00.0; 169(8), p. 962-8.
PMID: 19211621
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Oral Contraceptives And Postmenopausal Hormones And Risk Of Contralateral Breast Cancer Among Brca1 And Brca2 Mutation Carriers And Noncarriers: The Wecare Study
Authors: Figueiredo J.C. , Haile R.W. , Bernstein L. , Malone K.E. , Largent J. , Langholz B. , Lynch C.F. , Bertelsen L. , Capanu M. , Concannon P. , et al. .
Source: Breast Cancer Research And Treatment, 2010 Feb; 120(1), p. 175-83.
PMID: 19597986
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A Post-hoc Unweighted Analysis Of Counter-matched Case-control Data
Authors: Rakovski C. , Langholz B. .
Source: The International Journal Of Biostatistics, 2015 Nov; 11(2), p. 223-32.
PMID: 26351961
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