title: 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.
  
  
  METHODS
  Retrospective cohort study (GENE-RAD-RISK).
  
  
  METHODS
  Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands,
  
  
  METHODS
  1993 female carriers of BRCA1/2 mutations recruited in 2006-09.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Netherlands Cancer Institute, Department of Epidemiology and Biostatistics, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Pijpe
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Ausrele
authors.initials: A
authors.lastname: Kesminiene
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cardis
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Debra
authors.initials: D
authors.lastname: Frost
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.forename: Joan
authors.initials: J
authors.lastname: Paterson
authors.forename: Peggy
authors.initials: P
authors.lastname: Manders
authors.forename: Christi J
authors.initials: CJ
authors.lastname: van Asperen
authors.forename: Margreet G E M
authors.initials: MG
authors.lastname: Ausems
authors.forename: Hanne
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thierry-Chef
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.forename: David
authors.initials: D
authors.lastname: Goldgar
authors.forename: Matti A
authors.initials: MA
authors.lastname: Rookus
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
mesh_terms: D000328:Adult; D000367:Age Factors; D001940:Breast / Q000528:radiation effects; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008327:Mammography / Q000009:adverse effects*; D008875:Middle Aged; D009154:Mutation / Q000528:radiation effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult