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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Andrieu
Nadine
N
Institut National de la Santé et de la Recherche Médicale Emi00-06, Paris, France.
Easton
Douglas F
DF
Chang-Claude
Jenny
J
Rookus
Matti A
MA
Brohet
Richard
R
Cardis
Elisabeth
E
Antoniou
Antonis C
AC
Wagner
Teresa
T
Simard
Jacques
J
Evans
Gareth
G
Peock
Susan
S
Fricker
Jean-Pierre
JP
Nogues
Catherine
C
Van't Veer
Laura
L
Van Leeuwen
Flora E
FE
Goldgar
David E
DE
D000328:Adult; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D015331:Cohort Studies; D005060:Europe; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008327:Mammography / Q000009:adverse effects*; D008403:Mass Screening / Q000009:adverse effects*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires