title: Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study.
abstract: BACKGROUND
  Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies.
  
  
  METHODS
  We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework.
  
  
  RESULTS
  There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had ever used OC were at a significantly reduced risk of developing ovarian cancer (hazard ratio, 0.52; 95% confidence intervals, 0.37-0.73; P = 0.0002) and increasing duration of OC use was associated with a reduced ovarian cancer risk (P trend = 0.0004). The protective effect of OC use for BRCA1 mutation carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive conclusions.
  
  
  CONCLUSIONS
  The results provide further confirmation that OC use, number of full-term pregnancies, and tubal ligation are associated with ovarian cancer risk in BRCA1 carriers to a similar relative extent as in the general population.
authors.affiliation: Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK. antonis@srl.cam.ac.uk
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Matti
authors.initials: M
authors.lastname: Rookus
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.forename: Richard
authors.initials: R
authors.lastname: Brohet
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Margaret
authors.initials: M
authors.lastname: Cook
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Catherine
authors.initials: C
authors.lastname: Nogues
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Paul
authors.initials: P
authors.lastname: Gesta
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Margreet G E M
authors.initials: MG
authors.lastname: Ausems
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldes
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Edith
authors.initials: E
authors.lastname: Olah
authors.forename: Christine
authors.initials: C
authors.lastname: Fürhauser
authors.forename: Hakan
authors.initials: H
authors.lastname: Olsson
authors.forename: Brita
authors.initials: B
authors.lastname: Arver
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010298:Parity; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors; D013246:Sterilization, Tubal
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D003276:Contraceptives, Oral