Background.In recent years, numerous studies have assessed the prevalence of germline mutations inBRCA1andBRCA2genes in various cohorts. We here extensively investigated the prevalence and geographical distribution ofBRCA1-2mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence ofBRCA1-2germline 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 forBRCA1-2mutations by DHPLC analysis and DNA sequencing. Association ofBRCA1andBRCA2mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.Results and Conclusion.Overall, 8BRCA1and 5BRCA2deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found inBRCA2gene. The geographical distribution ofBRCA1-2mutations 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 aBRCA2 c.8764_8765delAGmutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (whereBRCA2mutations are still more common thanBRCA1mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (whereBRCA1mutations 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 ofBRCA1-2germline mutations.

A Role ofBRCA1andBRCA2germline mutations in breast cancer susceptibility within Sardinian population / Tanda, Francesco; Palomba, Grazia; Loi, Angela; Uras, Antonella; Fancello, Patrizia; Piras, Giovanna; Cossu, Antonio; Budroni, Mario; Contu, Antonio; Farris, Antonio; Orrù, Sandra; Floris, Carlo; Pisano, Marina; Lovicu, Mario; Santona, Maria Cristina; Landriscina, Gennaro; Crisponi, Laura; Palmieri, Giuseppe; Monne, Maria; Gabbas, Attilio. - In: BMC CANCER. - ISSN 1471-2407. - 9:245(2009), pp. 1-10. [10.1186/1471-2407-9-245]

A Role ofBRCA1andBRCA2germline mutations in breast cancer susceptibility within Sardinian population

Tanda, Francesco;Cossu, Antonio;Farris, Antonio;Floris, Carlo;Palmieri, Giuseppe;
2009-01-01

Abstract

Background.In recent years, numerous studies have assessed the prevalence of germline mutations inBRCA1andBRCA2genes in various cohorts. We here extensively investigated the prevalence and geographical distribution ofBRCA1-2mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence ofBRCA1-2germline 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 forBRCA1-2mutations by DHPLC analysis and DNA sequencing. Association ofBRCA1andBRCA2mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.Results and Conclusion.Overall, 8BRCA1and 5BRCA2deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found inBRCA2gene. The geographical distribution ofBRCA1-2mutations 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 aBRCA2 c.8764_8765delAGmutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (whereBRCA2mutations are still more common thanBRCA1mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (whereBRCA1mutations 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 ofBRCA1-2germline mutations.
2009
A Role ofBRCA1andBRCA2germline mutations in breast cancer susceptibility within Sardinian population / Tanda, Francesco; Palomba, Grazia; Loi, Angela; Uras, Antonella; Fancello, Patrizia; Piras, Giovanna; Cossu, Antonio; Budroni, Mario; Contu, Antonio; Farris, Antonio; Orrù, Sandra; Floris, Carlo; Pisano, Marina; Lovicu, Mario; Santona, Maria Cristina; Landriscina, Gennaro; Crisponi, Laura; Palmieri, Giuseppe; Monne, Maria; Gabbas, Attilio. - In: BMC CANCER. - ISSN 1471-2407. - 9:245(2009), pp. 1-10. [10.1186/1471-2407-9-245]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/264891
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