BRCA1 mutations in Spanish women with early-onset breast cancer

BACKGROUND: Germline mutations in the BRCA1 gene have been associated with familiar breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutatio ns. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years. PATIENTS AND METHODS: We analyzed genomic DNA samples of 159 women with ear ly-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cas es with mutations described in the literature were screened. Analysis invol ved polymerase chain reaction (PCR), single-strand conformation polymorphis ms (SSCP) and direct sequencing. RESULTS: Three germline BRCA1 mutations were identified, one of them not pr eviously described. Two mutations were found in women with familial hystory of breast cancer. Five additional rare variants and polymorphisms were als o detected. CONCLUSIONS: The absence of recurrent mutations or mutations detected in ot her countries, except for the 185delAG mutation, present in Ashkenazim popu lation, shows the influence of ethnic and geographic origin of population s tudied, and illustrates the difficulties of stablishing DNA-based screening tests for hereditary breast cancer.