title: BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients.
abstract: BACKGROUND
  A family history of prostate cancer (PrCa) is a strong risk factor for the disease, indicating that inherited factors are important in this disease. We previously estimated that about 2% of PrCa cases diagnosed ≤ 55 years harbour a BRCA2 mutation and PrCa among BRCA2 carriers has been shown to be more aggressive, with poorer survival.
  
  
  METHODS
  To further evaluate the role of BRCA2 in PrCa predisposition, we screened 1864 men with PrCa aged between 36 and 88 years. We analysed the BRCA2 gene using a novel high-throughput multiplex fluorescence heteroduplex detection system developed for the ABI3130xl genetic analyzer.
  
  
  RESULTS
  We identified 19 protein-truncating mutations, 3 in-frame deletions and 69 missense variants of uncertain significance (UV) in our sample set. All the carriers of truncating mutations developed PrCa at ≤ 65 years, with a prevalence of BRCA2 mutation of 1.20% for cases in this age group.
  
  
  CONCLUSIONS
  Based on the estimated frequency of BRCA2 mutations in the United Kingdom we estimate that germline mutations in the BRCA2 gene confer an ∼ 8.6-fold increased risk of PrCa by age 65, corresponding to an absolute risk of ∼ 15% by age 65. These results suggest that routine testing of early onset PrCa cases for germline BRCA2 mutations will further help to refine the prevalence and risk associated with BRCA2 mutations and may be useful for guiding management options.
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, Sutton SM2 5NG, UK. zsofia.kote-jarai@icr.ac.uk
authors.forename: Z
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: D
authors.initials: D
authors.lastname: Leongamornlert
authors.forename: E
authors.initials: E
authors.lastname: Saunders
authors.forename: M
authors.initials: M
authors.lastname: Tymrakiewicz
authors.forename: E
authors.initials: E
authors.lastname: Castro
authors.forename: N
authors.initials: N
authors.lastname: Mahmud
authors.forename: M
authors.initials: M
authors.lastname: Guy
authors.forename: S
authors.initials: S
authors.lastname: Edwards
authors.forename: L
authors.initials: L
authors.lastname: O'Brien
authors.forename: E
authors.initials: E
authors.lastname: Sawyer
authors.forename: A
authors.initials: A
authors.lastname: Hall
authors.forename: R
authors.initials: R
authors.lastname: Wilkinson
authors.forename: T
authors.initials: T
authors.lastname: Dadaev
authors.forename: C
authors.initials: C
authors.lastname: Goh
authors.forename: D
authors.initials: D
authors.lastname: Easton
authors.forename: D
authors.initials: D
authors.lastname: Goldgar
authors.forename: R
authors.initials: R
authors.lastname: Eeles
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics*; D016019:Survival Analysis