Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK)

Objective To estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations. Design Retrospective cohort study (GENE-RAD-RISK). Setting Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands, Participants 1993 female carriers of BRCA1/2 mutations recruited in 2006-09. Main outcome measure Risk of breast cancer estimated with a weighted Cox proportional hazards model with a time dependent individually estimated cumulative breast dose, based on nominal estimates of organ dose and frequency of self reported diagnostic procedures. To correct for potential survival bias, the analysis excluded carriers who were diagnosed more than five years before completion of the study questionnaire. Results In carriers of BRCA1/2 mutations any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of breast cancer (hazard ratio 1.90, 95% confidence interval 1.20 to 3.00), with a dose-response pattern. The risks by quarter of estimated cumulative dose <0.0020 Gy, ≥0.0020-0.0065 Gy, ≥0.0066-0.0173 Gy, and ≥0.0174 Gy were 1.63 (0.96 to 2.77), 1.78 (0.88 to 3.58), 1.75 (0.72 to 4.25), and 3.84 (1.67 to 8.79), respectively. Analyses on the different types of diagnostic procedures showed a pattern of increasing risk with increasing number of radiographs before age 20 and before age 30 compared with no exposure. A history of mammography before age 30 was also associated with an increased risk of breast cancer (hazard ratio 1.43, 0.85 to 2.40). Sensitivity analysis showed that this finding was not caused by confounding by indication of family history. Conclusion In this large European study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation before age 30 was associated with an increased risk of breast cancer at dose levels considerably lower than those at which increases have been found in other cohorts exposed to radiation. The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations.

[1]  F. V. van Leeuwen,et al.  Validation study suggested no differential misclassification of self-reported mammography history in BRCA1/2 mutation carriers. , 2011, Journal of clinical epidemiology.

[2]  D. Richardson,et al.  Fitting general relative risk models for survival time and matched case-control analysis. , 2010, American journal of epidemiology.

[3]  M. J. van de Vijver,et al.  Radiation-associated breast tumors display a distinct gene expression profile. , 2010, International journal of radiation oncology, biology, physics.

[4]  L. J. Veer,et al.  Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers , 2010, Breast Cancer Research and Treatment.

[5]  F. Leeuwen,et al.  Reliability of self-reported diagnostic radiation history in BRCA1/2 mutation carriers , 2010, European Journal of Epidemiology.

[6]  Simon Bouffler,et al.  Assessing cancer risks of low-dose radiation , 2009, Nature Reviews Cancer.

[7]  J. Lubiński,et al.  Early radiation exposures and BRCA1-associated breast cancer in young women from Poland , 2008, Breast Cancer Research and Treatment.

[8]  M. Hauptmann,et al.  Polymorphisms in Apoptosis- and Proliferation-Related Genes, Ionizing Radiation Exposure, and Risk of Breast Cancer among U.S. Radiologic Technologists , 2007, Cancer Epidemiology Biomarkers & Prevention.

[9]  Giovanni Parmigiani,et al.  Meta-analysis of BRCA1 and BRCA2 penetrance. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  K. Offit,et al.  Effect of Mammography on Breast Cancer Risk in Women with Mutations in BRCA1 or BRCA2 , 2006, Cancer Epidemiology Biomarkers & Prevention.

[11]  S. Boulton.  Cellular functions of the BRCA tumour-suppressor proteins. , 2006, Biochemical Society transactions.

[12]  J. Chang-Claude,et al.  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. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  P. Møller,et al.  Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. , 2006, The Lancet. Oncology.

[14]  Division on Earth.  Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2 , 2006 .

[15]  J. Chang-Claude,et al.  A weighted cohort approach for analysing factors modifying disease risks in carriers of high‐risk susceptibility genes , 2005, Genetic epidemiology.

[16]  K C Young,et al.  Radiation doses received in the UK Breast Screening Programme in 2001 and 2002. , 2005, The British journal of radiology.

[17]  Christine A Erdmann,et al.  Radiation and breast cancer: a review of current evidence , 2004, Breast Cancer Research.

[18]  Yoshio Miki,et al.  Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage , 2004, Cancer science.

[19]  S. Powell,et al.  Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation , 2003, Oncogene.

[20]  A. Localio,et al.  Validation of self-reported screening mammography histories among women with and without breast cancer. , 2003, American journal of epidemiology.

[21]  Lso,et al.  Ionising radiation exposure in the Netherlands , 2003 .

[22]  J. Hopper,et al.  Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. , 2003, American journal of human genetics.

[23]  Michael J. Allison,et al.  Comparison of documented and recalled histories of exposure to diagnostic x-rays in case-control studies of thyroid cancer. , 2003, American journal of epidemiology.

[24]  C. Land,et al.  Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990. , 1987, Radiation research.

[25]  S. Preston‐Martin,et al.  RADIATION EXPOSURE FROM DIAGNOSTIC IMAGING: AGREEMENT BETWEEN SELF-REPORT AND MEDICAL RECORDS , 2002, Health physics.

[26]  Erik Holmberg,et al.  Radiation Effects on Breast Cancer Risk: A Pooled Analysis of Eight Cohorts , 2002, Radiation research.

[27]  Ashok R Venkitaraman,et al.  Cancer Susceptibility and the Functions of BRCA1 and BRCA2 , 2002, Cell.

[28]  H. Kampinga,et al.  BRCA1 and BRCA2 heterozygosity and repair of X-ray-induced DNA damage , 2002, International journal of radiation biology.

[29]  K C Young,et al.  Radiation doses received in the UK Breast Screening Programme in 1997 and 1998. , 2000, The British journal of radiology.

[30]  S. Koscielny,et al.  The Example of Breast Cancer , 1999 .

[31]  G R Howe,et al.  Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer mortality in the atomic bomb survivors study. , 1995, Radiation research.

[32]  C. Land.  Studies of cancer and radiation dose among atomic bomb survivors. The example of breast cancer. , 1995, JAMA.

[33]  C. Land,et al.  Incidence of Female Breast Cancer among Atomic Bomb Survivors, Hiroshima and Nagasaki, 1950–1990 , 2003, Radiation research.

[34]  L. Bernstein,et al.  A dental x-ray validation study. Comparison of information from patient interviews and dental charts. , 1985, American journal of epidemiology.

[35]  C. Land.  Low‐dose radiation–a cause of breast cancer? , 1980, Cancer.

[36]  S. Kiestra,et al.  [Radiation dosage in fluoroscopy at a consultation office for tuberculosis control]. , 1961, Nederlands tijdschrift voor geneeskunde.

[37]  Sickenga Fn.  [Observations on radiation hazards, with special reference to roentgen examinations of tuberculosis]. , 1959 .

[38]  F. N. Sickenga.  [Observations on radiation hazards, with special reference to roentgen examinations of tuberculosis]. , 1959, Nederlands tijdschrift voor geneeskunde.