Spectrum and prevalence of BRCA 1 and BRCA 2 germline mutations in Sardinian patients with breast carcinoma through hospital‐based screening

Abstract BACKGROUND Factors that are predictive of carrying BRCA 1 and BRCA 2 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 BRCA 1/2 mutations by denaturing high‐performance liquid chromatography and DNA sequencing. RESULTS Three deleterious germline BRCA 1/2 mutations were detected in 15 of 102 families (14.7%), including 13 families (86.7%) with BRCA 2 mutations and 2 families (13.3%) with BRCA 1 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 BRCA 1/2 mutations (48.6 yrs) compared with the age of patients who had no detectable mutation (52.9 yrs; P = 0.039). Moreover, BRCA 1/2 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 BRCA 2 mutations were approximately 6 times more prevalent than BRCA 1 mutations. A diagnosis of breast carcinoma before age 50 years, ovarian carcinoma, male breast carcinoma, and 3 affected generations all were associated significantly with BRCA 1/2 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 BRCA 1/2 mutations may be useful in counseling patients about undergoing genetic testing. Cancer 2005. © 2005 American Cancer Society.