title: Familial prostate cancer: the damage done and lessons learnt.
abstract: BACKGROUND
  A 51-year-old French Canadian man presented to his family physician owing to an extensive family history of prostate cancer in five brothers, his father and two paternal uncles. His serum PSA level was 4.9 ng/ml and a six-core biopsy revealed the presence of a prostate adenocarcinoma with a Gleason score of 7 (3+4). He was treated with radical prostatectomy. Repeat PSA tests revealed a gradual rise in PSA levels despite androgen deprivation therapy with bicalutamide and goserelin over the course of 3 years. Genetic evaluation was undertaken in view of his personal and family history. The proband died at the age of 58 years of widespread metastasis.
  
  
  METHODS
  PSA testing, six-core biopsy, genetic counselling and mutation analysis for French Canadian founder mutations in the BRCA1 and BRCA2 genes, histopathological review of tumour tissue from family members, examination of loss of heterozygosity at the BRCA2 gene locus, immunohistochemistry to determine the expression of the ERG nuclear oncoprotein in prostate tumours, genotyping with eight selected risk-associated single nucleotide polymorphisms, Doppler ultrasonography of the leg, CT of the abdomen and pelvis with intravenous and oral contrast, chest CT with intravenous contrast for the assessment of metastatic prostate cancer, genetic testing for the G84E variant in the HOXB13 gene.
  
  
  METHODS
  Early-onset and aggressive prostate cancer associated with a nonsense French Canadian BRCA2 founder mutation, c.5857G>T (p.Glu1953(*)).
  
  
  RESULTS
  Radical prostatectomy, hormone therapy with bicalutamide and goserelin, palliative chemotherapy initially with docetaxel plus prednisone then with mitoxantrone plus prednisone, as well as genetic counselling and testing for the proband and his family members.
authors: Department of Medical Genetics, Research Institute of McGill University Health Centre, Montreal, QC H3G 1A4, Canada.
authors: Nassim
authors: N
authors: Taherian
authors: Nancy
authors: N
authors: Hamel
authors: Louis R
authors: LR
authors: Bégin
authors: Tarek A
authors: TA
authors: Bismar
authors: David E
authors: DE
authors: Goldgar
authors: Bing-Jian
authors: BJ
authors: Feng
authors: William D
authors: WD
authors: Foulkes
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics; D017809:Fatal Outcome; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins