title: A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population.
abstract: BACKGROUND
  In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated.
  
  
  METHODS
  Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.
  
  
  CONCLUSIONS
  Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.
authors.affiliation: Istituto Chimica Biomolecolare-CNR, Trav. La Crucca - Baldinca Li Punti, 07100 Sassari, Italy. graziap68@yahoo.it
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.forename: Angela
authors.initials: A
authors.lastname: Loi
authors.forename: Antonella
authors.initials: A
authors.lastname: Uras
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fancello
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piras
authors.forename: Attilio
authors.initials: A
authors.lastname: Gabbas
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Antonio
authors.initials: A
authors.lastname: Contu
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Sandra
authors.initials: S
authors.lastname: Orrù
authors.forename: Carlo
authors.initials: C
authors.lastname: Floris
authors.forename: Marina
authors.initials: M
authors.lastname: Pisano
authors.forename: Mario
authors.initials: M
authors.lastname: Lovicu
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Santona
authors.forename: Gennaro
authors.initials: G
authors.lastname: Landriscina
authors.forename: Laura
authors.initials: L
authors.lastname: Crisponi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.forename: Maria
authors.initials: M
authors.lastname: Monne
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D012008:Recurrence