Effect of Chest X-Rays on the Risk of Breast Cancer Among BRCA1/2 Mutation
Carriers in the International BRCA1/2 Carrier Cohort Study.
Andrieu N, Easton DF, Chang-Claude J, Rookus MA, Brohet R, Cardis E, Antoniou
AC, Wagner T, Simard J, Evans G, Peock S, Fricker JP, Nogues C, Van't Veer L,
Van Leeuwen FE, Goldgar DE.
L'Institut National de la Sante et de la Recherche Medicale Emi00-06 et
Service de Biostatistique de l'Institut Curie, Paris; International Agency for
Research on Cancer, Lyon; Centre Paul Strauss, Strasbourg; Centre Rene Huguenin,
Saint Cloud, France; Cancer Research UK, Genetic Epidemiology Unit, Department
of Public Health and Primary Care, University of Cambridge, Cambridge;
Department of Genetics, St Mary's Hospital, Manchester, United Kingdom; Division of
Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany;
Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer
Institute, Amsterdam, the Netherlands; Division of Senology, Medical University of
Vienna and Private Trust for Breast Health, Vienna, Austria; Laboratoire de
Genomique des Cancers, Laval University, Quebec City, Quebec, Canada; and
Department of Medical Informatics, University of Utah, Salt Lake City, UT; and the
Gene Etude Prospective Sein Ovaire (GENEPSO), Gen en Omgeving studie van de
werkgroep Hereditiair Borstkanker Onderzoek Nederland (GEO-HEBON), and the
International BRCA1/2 Carrier Cohort Study (IBCCS) Collaborators' Group.
PURPOSE: Women who carry germline mutations in the BRCA1 and BRCA2 genes are
at greatly increased risk of breast cancer (BC). Numerous studies have shown
that moderate to high doses of ionizing radiation are a risk factor for BC.
Because of the role of the BRCA proteins in DNA repair, we hypothesized that BRCA
carriers might be more sensitive to ionizing radiation than women in the
PATIENTS AND METHODS: A retrospective cohort study of 1,601
female BRCA1/2 carriers was performed. Risk of breast cancer from exposure to
chest x-rays, as assessed by questionnaire data, was analyzed using a weighted
Cox proportional hazards model.
RESULTS: In this cohort, any reported exposure
to chest x-rays was associated with an increased risk of BC (hazard ratio [HR]
= 1.54; P = .007).
This risk was increased in carrier women aged 40 years and
younger (HR = 1.97; P < .001) and in women born after 1949 (HR = 2.56; P <
.001), particularly those exposed only before the age of 20 years (HR = 4.64; P <
CONCLUSION: In our series of BRCA carriers, we detected a relatively
large effect on BC risk with a level of radiation exposure that is at least an
order of magnitude lower than in previously studied medical radiation-exposed
Although part of this increase may be attributable to recall bias,
the observed patterns of risk in terms of age at exposure and attained age are
consistent with those found in previous studies.
If confirmed, the results
have important implications for the use of x-ray imaging in young BRCA1/2
J Clin Oncol. 2006 Jun 26; [Epub ahead of print]
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