title: Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital-based screening.
abstract: BACKGROUND
  Factors that are predictive of carrying BRCA1 and BRCA2 germline mutations in patients with breast carcinoma are awaited widely. The genetically homogeneous Sardinian population may be useful for defining the role of such genetic alterations further through a clinical evaluation program.
  
  
  METHODS
  One hundred two of 659 patients with breast carcinoma (15.5%) who were collected consecutively had a family history of breast carcinoma and were screened for BRCA1/2 mutations by denaturing high-performance liquid chromatography and DNA sequencing.
  
  
  RESULTS
  Three deleterious germline BRCA1/2 mutations were detected in 15 of 102 families (14.7%), including 13 families (86.7%) with BRCA2 mutations and 2 families (13.3%) with BRCA1 mutations. A single variant, BRCA2-8765delAG, was the most recurrent mutation in the series and was found in 12 of 102 families (11.8%) and in 18 of 657 patients (2.7%). The average age at diagnosis was significantly younger in families with BRCA1/2 mutations (48.6 yrs) compared with the age of patients who had no detectable mutation (52.9 yrs; P = 0.039). Moreover, BRCA1/2 mutations were found at a significantly higher rate in families who had at least 1 member with ovarian carcinoma or male breast carcinoma (5 of 12 families; 41.7%) than in families without such an association (10 of 90 families; 11.1%; P = 0.003).
  
  
  CONCLUSIONS
  BRCA2 mutations were approximately 6 times more prevalent than BRCA1 mutations. A diagnosis of breast carcinoma before age 50 years, ovarian carcinoma, male breast carcinoma, and 3 affected generations all were associated significantly with BRCA1/2 mutations. Although the current findings provided further support for the hypothesis that additional breast carcinoma susceptibility genes remain to be identified, such indicators of the presence of BRCA1/2 mutations may be useful in counseling patients about undergoing genetic testing.
authors.affiliation: Institute of Biomolecular Chemistry-Sezione di Sassari, CNR, Alghero (SS), Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.forename: Marina
authors.initials: M
authors.lastname: Pisano
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Maria F
authors.initials: MF
authors.lastname: Dedola
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Antonio
authors.initials: A
authors.lastname: Contu
authors.forename: Paola
authors.initials: P
authors.lastname: Baldinu
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D015995:Prevalence