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Grant Details

Grant Number: 5R01CA097397-05 Interpret this number
Primary Investigator: Bernstein, Jonine
Organization: Sloan-Kettering Inst Can Res
Project Title: Interaction of Radiation, BRCA1/2, and Breast Cancer
Fiscal Year: 2006
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Abstract

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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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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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 DC, Stovall M, Smith SA, Boice JD Jr, Shore RE, Bernstein L, Lynch CF, Zhang X, Bernstein JL
Source: Biometrics, 2009 Jun;65(2), p. 599-608.
EPub date: 2008 Jul 18.
PMID: 18647297
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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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