title: Familial breast cancer genetic testing in the West of Ireland.
abstract: OBJECTIVE
  The majority of hereditary breast and ovarian cancers are associated with highly penetrant mutations in two genes: BRCA 1 and 2. Our aim was to investigate the prevalence and types of BRCA mutations in patients from the West of Ireland.
  
  
  METHODS
  A retrospective cohort study was undertaken that included all patients from the counties, Mayo, Sligo, Galway, Roscommon, and Clare, who were referred to the National Centre for Medical Genetics (NCMG) for testing for mutations in BRCA 1 or 2 between 2000 and 2010. Data including age, symptoms, family history, Manchester score, and test results were recorded and analysed using SPSS.
  
  
  RESULTS
  The NCMG received 380 referrals from the Western seaboard, including 148 for diagnostic testing and 232 for predictive evaluation. Sixty-five patients did not attend for assessment. Two hundred and fifty-six patients fulfilled criteria for genetic counselling, which was accepted by 184, of whom 127 proceeded to testing. Predictive tests were more often declined than diagnostic [41 (46 %) vs. 16 (17 %)]. Ten mutations in BRCA 1 were identified in 20 patients (15 families), including Exon 1-23del (3 families); Exon 14-20del (2 families) and E143X (2 families). Six mutations in BRCA 2 were identified in 15 patients (12 families) including 8525delC (n = 2 families) and 8205-1G>C (n = 3 families). Patients with positive results had significantly higher Manchester scores than those with negative tests [median 25.5 (12-48) vs. 20 (8-37), p = 0.042, Mann-Whitney U test].
  
  
  CONCLUSIONS
  To identify patients with highly penetrant variants, referrals should be made with strict adherence to guidelines. Counselling should be individualised to counteract intrinsic psychological barriers to testing.
authors.affiliation: Discipline of Surgery, Clinical Sciences Institute, National University of Ireland, Galway, Ireland, terri.mcveigh@gmail.com.
authors.forename: T P
authors.initials: TP
authors.lastname: McVeigh
authors.forename: R
authors.initials: R
authors.lastname: Irwin
authors.forename: N
authors.initials: N
authors.lastname: Cody
authors.forename: N
authors.initials: N
authors.lastname: Miller
authors.forename: T
authors.initials: T
authors.lastname: McDevitt
authors.forename: K J
authors.initials: KJ
authors.lastname: Sweeney
authors.forename: A
authors.initials: A
authors.lastname: Green
authors.forename: M J
authors.initials: MJ
authors.lastname: Kerin
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001943:Breast Neoplasms / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D018567:Breast Neoplasms, Male / Q000175:diagnosis / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D010342:Patient Acceptance of Health Care / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D015995:Prevalence; D012189:Retrospective Studies; D055815:Young Adult