title: Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis.
abstract: BACKGROUND
  The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours.
  
  
  METHODS
  Two cohorts were compared: one was a group with young-onset PrCa, tested for germline BRCA2 mutations (6 of 263 cases had a germline BRAC2 mutation), and the second was a validation set consisting of a clinical set from Manchester of known BRCA2 mutuation carriers (15 cases) with PrCa. Survival data were compared with a control series of patients in a single clinic as determined by Kaplan-Meier estimates. Loss of heterozygosity was tested for in the DNA of tumour tissue of the young-onset group by typing four microsatellite markers that flanked the BRCA2 gene, followed by sequencing.
  
  
  RESULTS
  Median survival of all PrCa cases with a germline BRCA2 mutation was shorter at 4.8 years than was survival in controls at 8.5 years (P=0.002). Loss of heterozygosity was found in the majority of tumours of BRCA2 mutation carriers. Multivariate analysis confirmed that the poorer survival of PrCa in BRCA2 mutation carriers is associated with the germline BRCA2 mutation per se.
  
  
  CONCLUSIONS
  BRCA2 germline mutation is an independent prognostic factor for survival in PrCa. Such patients should not be managed with active surveillance as they have more aggressive disease.
authors.affiliation: Oncogenetics team, Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5PT, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Edwards
authors.forename: D G R
authors.initials: DG
authors.lastname: Evans
authors.forename: Q
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authors.lastname: Hope
authors.forename: A R
authors.initials: AR
authors.lastname: Norman
authors.forename: Y
authors.initials: Y
authors.lastname: Barbachano
authors.forename: S
authors.initials: S
authors.lastname: Bullock
authors.forename: Z
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authors.lastname: Kote-Jarai
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authors.lastname: Meitz
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authors.lastname: Falconer
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authors.lastname: Fisher
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authors.lastname: Guy
authors.forename: S G
authors.initials: SG
authors.lastname: Jhavar
authors.forename: A L
authors.initials: AL
authors.lastname: Hall
authors.forename: L T
authors.initials: LT
authors.lastname: O'Brien
authors.forename: B N
authors.initials: BN
authors.lastname: Gehr-Swain
authors.forename: R A
authors.initials: RA
authors.lastname: Wilkinson
authors.forename: M S
authors.initials: MS
authors.lastname: Forrest
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: A T
authors.initials: AT
authors.lastname: Ardern-Jones
authors.forename: E C
authors.initials: EC
authors.lastname: Page
authors.forename: D F
authors.initials: DF
authors.lastname: Easton
authors.forename: R A
authors.initials: RA
authors.lastname: Eeles
mesh_terms: D000328:Adult; D000368:Aged; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D016019:Survival Analysis