A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population.
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.
Palomba
Grazia
G
Istituto Chimica Biomolecolare-CNR, Trav. La Crucca - Baldinca Li Punti, 07100 Sassari, Italy. graziap68@yahoo.it
Loi
Angela
A
Uras
Antonella
A
Fancello
Patrizia
P
Piras
Giovanna
G
Gabbas
Attilio
A
Cossu
Antonio
A
Budroni
Mario
M
Contu
Antonio
A
Tanda
Francesco
F
Farris
Antonio
A
Orrù
Sandra
S
Floris
Carlo
C
Pisano
Marina
M
Lovicu
Mario
M
Santona
Maria Cristina
MC
Landriscina
Gennaro
G
Crisponi
Laura
L
Palmieri
Giuseppe
G
Monne
Maria
M
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