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

Grant Number: 5R01CA097397-05 Interpret this number
Primary Investigator: Bernstein, Jonine
Organization: Sloan-Kettering Inst Can Research
Project Title: Interaction of Radiation, BRCA1/2, and Breast Cancer
Fiscal Year: 2006
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DESCRIPTION (provided by applicant): Deficiencies in cellular response to DNA damage can predispose to cancer. However, the gene-environment interactions that may be involved in the etiology of these cancers are poorly understood. One important environmental cause of DNA damage is exposure to ionizing radiation leading to the formation of DNA double-strand breaks (DSB). Recent evidence demonstrates that three genes in which mutations predispose to breast cancer, BRCA1/2 and ATM have complex interactions with each other and are essential for the normal cellular response to DSBs. Therefore, interaction between alleles at these loci may have important effects on breast cancer risk, in general, and radiation-induced breast cancer, in particular. To delineate the roles of radiation exposure and genetic predisposition in the etiology of breast cancer, we propose to determine the prevalence of BRCA1/2 mutations in a well characterized population-based sample of 2100 women with breast cancer for whom blood samples have already been obtained and ATM mutation status already determined. Our study hypothesis is that the incidence of contralateral breast cancer will be increased among women who are carriers of mutant BRCA1 or BRCA2 alleles and who received RT as part of treatment for first primary breast cancer. The 700 cases are women with bilateral breast cancer individually countermatched to two controls, women with unilateral breast cancer. Our specific aims are: Aim #1. To test for germline BRCA1/2 mutations in a population-based sample of young women with unilateral and bilateral breast cancer, using a staged approach with DHPLC screening followed by sequencing. Aim #2. To conduct analyses of gene-environment interactions for BRCA1/2 with a focus on radiation exposure. To achieve this aim, we will collect medical/treatment records and recreate the scatter radiation dose to the contralateral breast. Once our study has been completed, we will have established an outstanding resource for future studies of other putative breast cancer genes and environmental exposures, with a particular focus on radiation exposure.

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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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Statistical Methods For Analysis Of Radiation Effects With Tumor And Dose Location-specific Information With Application To The Wecare Study Of Asynchronous Contralateral Breast Cancer
Authors: Langholz B. , Thomas D.C. , Stovall M. , Smith S.A. , Boice J.D. , Shore R.E. , Bernstein L. , Lynch C.F. , Zhang X. , Bernstein J.L. .
Source: Biometrics, 2009 Jun; 65(2), p. 599-608.
PMID: 18647297
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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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