Originally published as JCO Early Release 10.1200/JCO.2005.03.3126 on June 26 2006

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Effect of Chest X-Rays on the Risk of Breast Cancer Among BRCA1/2 Mutation Carriers in the International BRCA1/2 Carrier Cohort Study: A Report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group

Nadine Andrieu, Douglas F. Easton, Jenny Chang-Claude, Matti A. Rookus, Richard Brohet, Elisabeth Cardis, Antonis C. Antoniou, Teresa Wagner, Jacques Simard, Gareth Evans, Susan Peock, Jean-Pierre Fricker, Catherine Nogues, Laura Van't Veer, Flora E. Van Leeuwen, David E. Goldgar

From L'Institut National de la Santé et de la Recherche Médicale Emi00-06 et Service de Biostatistique de l'Institut Curie, Paris; International Agency for Research on Cancer, Lyon; Centre Paul Strauss, Strasbourg; Centre René 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 Génomique des Cancers, Laval University, Québec City, Québec, 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

Address reprint requests to David E. Goldgar, Department of Dermatology, University of Utah School of Medicine, 30 N. Medical Dr, Salt Lake City, UT 84132; e-mail: david.goldgar{at}hsc.utah.edu

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 general population.

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 < .001).

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 cohorts. 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 carriers.

Supported by Grants No. SI2.328176 and SPC.2002482 from the European Commission (International BRCA1/2 Carrier Cohort Study); Cancer Research UK and The British Council (Epidemiological Study of BRCA1 and BRCA2 Mutation Carriers [EMBRACE]); Fondation de France and Ligue Nationale Contre le Cancer (GENEPSO); Dutch Cancer Society Grant No. NKI98-1854 (GEO-HEBON); and the Interdisciplinary Health Research International Team on Breast Cancer Susceptibility (INHERIT) project of the Canadian Institutes of Health Research.

The funding sources providing support for the International BRCA1/2 Carrier Cohort Study had no role in the design, data collection, and analysis of the data described in this article and had no role in the writing of the article and the decision to submit the paper for publication.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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