Open Access Highly Accessed Research article

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

Grazia Palomba1, Angela Loi2, Antonella Uras3, Patrizia Fancello3, Giovanna Piras3, Attilio Gabbas3, Antonio Cossu4, Mario Budroni4, Antonio Contu4, Francesco Tanda5, Antonio Farris5, Sandra Orrù6, Carlo Floris6, Marina Pisano1, Mario Lovicu2, Maria Cristina Santona7, Gennaro Landriscina7, Laura Crisponi2, Giuseppe Palmieri1 and Maria Monne3*

Author Affiliations

1 Istituto Chimica Biomolecolare-CNR, Trav. La Crucca – Baldinca Li Punti, 07100 Sassari, Italy

2 Istituto di Neurogenetica e Neurofarmacologia-CNR, Cittadella Universitaria di Cagliari, 09042 Monserrato, Italy

3 U. O. Ematologia, Ospedale San Francesco, Azienda USL3, via Mannironi, 08100 Nuoro, Italy

4 Azienda USL1, Via Monte Grappa, 07100 Sassari, Italy

5 Università di Sassari, Piazza Università, 07100 Sassari, Italy

6 Ospedale Oncologico A. Businco, Azienda USL8, Via Jenner, 09100 Cagliari, Italy

7 U.O. Oncologia, Ospedale C. Zonchello, Azienda USL3, via Mannironi, 08100 Nuoro, Italy

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BMC Cancer 2009, 9:245  doi:10.1186/1471-2407-9-245

Published: 20 July 2009



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.


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.

Results and Conclusion

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.