Journal article
Study design: evaluating gene-environment interactions in the etiology of breast cancer - the WECARE study
Breast cancer research : BCR, Vol.6(3), pp.R199-214
2004
DOI: 10.1186/bcr771
PMCID: PMC400669
PMID: 15084244
Abstract
Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated.
To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses.
Our study design improves the potential for detecting gene-environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case-control sets and enhanced our ability to detect radiation-genotype interactions.
Details
- Title: Subtitle
- Study design: evaluating gene-environment interactions in the etiology of breast cancer - the WECARE study
- Creators
- Jonine L Bernstein - Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY, USA. jonine.bernstein@mssm.eduBryan LangholzRobert W HaileLeslie BernsteinDuncan C ThomasMarilyn StovallKathleen E MaloneCharles F LynchJørgen H OlsenHoda Anton-CulverRoy E ShoreJohn D Boice JrGertrud S BerkowitzRichard A GattiSusan L TeitelbaumSusan A SmithBarry S RosensteinAnne-Lise Børresen-DalePatrick ConcannonW Douglas ThompsonWECARE study
- Resource Type
- Journal article
- Publication Details
- Breast cancer research : BCR, Vol.6(3), pp.R199-214
- Publisher
- England
- DOI
- 10.1186/bcr771
- PMID
- 15084244
- PMCID
- PMC400669
- ISSN
- 1465-5411
- eISSN
- 1465-542X
- Grant note
- R01 CA129639 / NCI NIH HHS U01 CA083178 / NCI NIH HHS R01-CA42949 / NCI NIH HHS R01 CA097397 / NCI NIH HHS U01-CA83178 / NCI NIH HHS R01-CA97397 / NCI NIH HHS R01 CA042949 / NCI NIH HHS
- Language
- English
- Date published
- 2004
- Academic Unit
- Epidemiology
- Record Identifier
- 9983996087202771
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