title: Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.
abstract: BACKGROUND
  Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.
  
  
  METHODS
  A prospective study involving women seen at a single family history clinic in Manchester, UK. Patients were excluded if they had ovarian cancer or oophorectomy prior to clinic. Follow-up was censored at the latest date of: 31/12/2010; ovarian cancer diagnosis; oophorectomy; or death. We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.
  
  
  RESULTS
  We studied 8005 women from 895 families. Women from BRCA2 mutation families showed a 17-fold increased risk of invasive ovarian cancer (relative risk (RR) 16.67; 95% CI 5.41 to 38.89). This risk increased to 50-fold in women from families with BRCA1 mutations (RR 50.00; 95% CI 26.62 to 85.50). No association was found for women in families tested negative for BRCA1/2, where there was 1 observed invasive ovarian cancer in 1613 women when 2.74 were expected (RR 0.37; 95% CI 0.01 to 2.03). There was no association with ovarian cancer in families untested for BRCA1/2 (RR 0.99; 95% CI 0.45 to 1.88).
  
  
  CONCLUSIONS
  This study showed no increased risk of ovarian cancer in families that tested negative for BRCA1/2 or were untested. These data help counselling women from BRCA1/2 negative families with breast cancer that their risk of invasive ovarian cancer is not higher than the general population.
authors.affiliation: Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UK.
authors.forename: Sarah Louise
authors.initials: SL
authors.lastname: Ingham
authors.forename: Jane
authors.initials: J
authors.lastname: Warwick
authors.forename: Iain
authors.initials: I
authors.lastname: Buchan
authors.forename: Sarah
authors.initials: S
authors.lastname: Sahin
authors.forename: Catherine
authors.initials: C
authors.lastname: O'Hara
authors.forename: Anthony
authors.initials: A
authors.lastname: Moran
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein
keywords: BRCA; Cancer: breast; Cancer: ovarian