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The first two authors contributed equally to this work.
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Original Article
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Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital-based screening
Article first published online: 26 JUL 2005
DOI: 10.1002/cncr.21298
Copyright © 2005 American Cancer Society
Additional Information
How to Cite
Palomba, G., Pisano, M., Cossu, A., Budroni, M., Dedola, M. F., Farris, A., Contu, A., Baldinu, P., Tanda, F. and Palmieri, G. (2005), Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital-based screening. Cancer, 104: 1172–1179. doi: 10.1002/cncr.21298
Publication History
- Issue published online: 31 AUG 2005
- Article first published online: 26 JUL 2005
- Manuscript Accepted: 31 MAR 2005
- Manuscript Revised: 16 MAR 2005
- Manuscript Received: 10 NOV 2004
Funded by
- Regione Autonoma della Sardegna
- Ricerca Finalizzata Ministero della Salute
- Fondazione Banco di Sardegna
- Associazione Italiana Ricerca sul Cancro
- Abstract
- Article
- References
- Cited By
Keywords:
- BRCA1 gene;
- BRCA2 gene;
- polymerase chain reaction;
- mutation analysis;
- genetic counseling;
- breast cancer risk
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. Cancer 2005. © 2005 American Cancer Society.