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

Abstract

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 ConclusionIn 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. IntroductionExposure to ionising radiation is an established risk factor for breast cancer in the general population, with exposures in childhood and adolescence conferring a greater risk than exposure in adulthood. 1 As BRCA1 and BRCA2 are involved in the repair of DNA double strand breaks, 2-6 which can be caused by ionising radiation, it has been hypothesised that carriers of BRCA1/2 mutations might have increased radiosensitivity. Results of the few studies 7-10 conducted so far on diagnostic radiation and risk of breast cancer among carriers have been inconsistent. Explanations for this inconsistency include differences in age at exposure and study limitations such as the investigation of a single type of diagnostic procedure (such as only chest radiography 7 8 or only mammography 9 10 ), a retrospective design with potential recall and/or survival bias, [7][8][9][10] or sometimes relatively small numbers. 8 9 In some countries the screening protocol for BRCA1/2 mutation carriers now recommends the avoidance of mammographic screening before age 30 and advises the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging (MRI)) as the main tool for surveillance at young ages.We report on the BRCA1/2 mutation carrier study arm of the GENE-RAD-RISK project, a large European cohort study designed to examine whether variations in specific DNA repair genes increase the risk of breast cancer associated with radiation. Although the present study has a retrospective design, the association between diagnostic radiation and breast cancer risk in BRCA1/2 mutation carriers is unlikely to be investigated p...

New challenges in high-energy particle radiobiology

“…In the analysis of cancer risk in children from 160 families irradiated in Israel after World War II for an epidemic of tinea capitis, it was found that the increased meningioma incidence in irradiated children was determined by a subgroup of only 17 families (11%), where 4 of 5 children developed meningioma. 105 In addition, the large European cohort study GENE-RAD-RISK 106 has recently concluded that in carriers of BRCA1/2 mutations, any exposure to diagnostic radiation before the age of 30 years is associated with an increased risk of breast cancer. The relative risk in the mutant carrier was 1.9 and increased with dose.…”

“…The relative risk in the mutant carrier was 1.9 and increased with dose. 106 Genetic predisposition may also drive the risk from exposure to charged particles. This is a critical issue for paediatric patients, a group that is often referred to proton therapy because much normal tissue can be spared compared with X-rays and, therefore, toxicity is reduced.…”

Role of Noninvasive Testing in the Clinical Evaluation of Women With Suspected Ischemic Heart Disease

“…For low-risk premenopausal women, alternative tests without radiation exposure (eg, ECG) or a no-testing strategy should be strongly considered. 40 Table 3 details the typical effective radiation dose for MPI, angiography, and CCTA. 35,41 Average background radiation exposure per year for a member of the US population is ≈3.1 mSv.…”

No strong evidence for increased risk of breast cancer 8–26 years after multiple mammograms in their 30s in females at moderate and high familial risk

“…This does not account for higher background risks of breast cancer or increased radiosensitivity suggested for BRCA1/BRCA2 carriers whose genetic defects give rise to impairment in DNA repair by homologous recombination, once the cell has lost both functioning copies of the gene. 15 However, it still remains to be shown that the cells which are heterozygous for a mutation are more radiosensitive. The current study is not powered to assess any effects in BRCA1/2 mutation carriers specifically, and as these females qualify for the more sensitive MRI screening, they may not need mammography.…”

“…Nevertheless, we would not advocate commencing mammography ,30, in line with current UK recommendations. 15 The lower sensitivity of mammography in younger females 16 should be taken into account in determining its potential risks and benefits in these females. There was also no evidence of a greater carcinogenic effect of radiation in those estimated at particularly high breast cancer risk (.30%).…”