title: Increased risk of male cancer and identification of a potential prostate cancer cluster region in BRCA2.
abstract: BACKGROUND
  The risk of cancer in men from BRCA1 and BRCA2 families is relevant to define to motivate genetic testing and optimize recommendations for surveillance.
  
  
  METHODS
  We assessed the risk of cancer in male mutation carriers and their first-degree relatives in 290 BRCA1 and BRCA2 families with comparison to matched controls with the aim to motivate genetic testing and optimize recommendations for surveillance.
  
  
  RESULTS
  Mutation carriers in BRCA1 families were not at increased risk of cancer, whereas mutation carriers in BRCA2 families were at increased risk of male breast cancer and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively. Breast cancer developed at a mean age of 59 years, typically as ER/PR positive ductal carcinomas. Prostate cancer developed at a mean age of 68 years, with Gleason scores ≥ 8 in 40% of the tumors. The hazard ratio for BRCA2-associated prostate cancer was 3.7 (p < 0.001) in mutation carriers and 3.1 (p = 0.001) in first-degree relatives. Of the 37 prostate cancers, 19 were linked to four BRCA2 mutations within a region defined by c.6373-c.6492. Individuals with mutations herein had a HR of 3.7 for prostate cancer compared to individuals with mutations outside of this region.
  
  
  CONCLUSIONS
  Male mutation carriers and first-degree relatives in BRCA2 families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of BRCA2.
authors.affiliation: a Department of Clinical Genetics , Vejle Hospital , Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Roed Nielsen
authors.affiliation: b HNPCC Register, Clinical Research Center, Copenhagen University Hospital , Hvidovre , Denmark.|c Department of Biostatistics , University of Copenhagen , Denmark.
authors.forename: Janne
authors.initials: J
authors.lastname: Petersen
authors.affiliation: b HNPCC Register, Clinical Research Center, Copenhagen University Hospital , Hvidovre , Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Therkildsen
authors.affiliation: d Department of Clinical Genetics , Aarhus University Hospital , Denmark.
authors.forename: Anne-Bine
authors.initials: AB
authors.lastname: Skytte
authors.affiliation: b HNPCC Register, Clinical Research Center, Copenhagen University Hospital , Hvidovre , Denmark.|e Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University , Lund , Sweden.
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D000367:Age Factors; D000368:Aged; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005190:Family; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012306:Risk