title: Germline BRCA1 mutations increase prostate cancer risk.
abstract: BACKGROUND
  Prostate cancer (PrCa) is one of the most common cancers affecting men but its aetiology is poorly understood. Family history of PrCa, particularly at a young age, is a strong risk factor. There have been previous reports of increased PrCa risk in male BRCA1 mutation carriers in female breast cancer families, but there is a controversy as to whether this risk is substantiated. We sought to evaluate the role of germline BRCA1 mutations in PrCa predisposition by performing a candidate gene study in a large UK population sample set.
  
  
  METHODS
  We screened 913 cases aged 36–86 years for germline BRCA1 mutation, with the study enriched for cases with an early age of onset. We analysed the entire coding region of the BRCA1 gene using Sanger sequencing. Multiplex ligation-dependent probe amplification was also used to assess the frequency of large rearrangements in 460 cases.
  
  
  RESULTS
  We identified 4 deleterious mutations and 45 unclassified variants (UV). The frequency of deleterious BRCA1 mutation in this study is 0.45%; three of the mutation carriers were affected at age 65 years and one developed PrCa at 69 years. Using previously estimated population carrier frequencies, deleterious BRCA1 mutations confer a relative risk of PrCa of ~3.75-fold, (95% confidence interval 1.02–9.6) translating to a 8.6% cumulative risk by age 65.
  
  
  CONCLUSIONS
  This study shows evidence for an increased risk of PrCa in men who harbour germline mutations in BRCA1. This could have a significant impact on possible screening strategies and targeted treatments.
authors.affiliation: Oncogenetics Team, The Institute of Cancer Research, Sutton SM2 5NG, UK.
authors.forename: D
authors.initials: D
authors.lastname: Leongamornlert
authors.forename: N
authors.initials: N
authors.lastname: Mahmud
authors.forename: M
authors.initials: M
authors.lastname: Tymrakiewicz
authors.forename: E
authors.initials: E
authors.lastname: Saunders
authors.forename: T
authors.initials: T
authors.lastname: Dadaev
authors.forename: E
authors.initials: E
authors.lastname: Castro
authors.forename: C
authors.initials: C
authors.lastname: Goh
authors.forename: K
authors.initials: K
authors.lastname: Govindasami
authors.forename: M
authors.initials: M
authors.lastname: Guy
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: 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
authors.forename: Z
authors.initials: Z
authors.lastname: Kote-Jarai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D012306:Risk