BRCA1 mutations in African Americans

The breast cancer predisposing gene, BRCA1, was analyzed for germline mutat ions in 45 African American families at high-risk for hereditary breast can cer. Patients were considered high-risk if they had a family history of the disease, early onset breast cancer, bilateral breast cancer, or breast and ovarian cancer. The entire BRCA1 coding and flanking intron regions have b een examined by single stranded conformation polymorphism analysis followed by sequencing of variant bands. Eleven different BRCA1 germline mutations/ variations were identified in 7 patients from the 45 high-risk families. Tw o pathogenic, protein-truncating mutations were detected in exon 11. A ten base pair tandem duplication, 943ins10, was present in a woman with breast and ovarian cancer whose first-degree relatives had prostate cancer. A four base pair deletion, 3450de14, was detected in a breast cancer patient with five cases of breast cancer in the family; two of the proband's sisters wi th breast cancer also carried the same mutation. Four amino acid substituti ons (Lys1183Arg, Leu1564Pro, Gln1785His, and Glu1794Asp) and four nucleotid e substitutions in intron 22 (IVS22+78 C/A, IVS22+67 T/C, IVS22+8 T/A and I VS22+7 T/C) were observed in patients and not in control subjects. One earl y onset breast cancer patient carried five distinct BRCA1 variations, two a mino acid substitutions and three substitutions in intron 22. An amino acid substitution in exon 11, Ser1140Gly, was identified in 3 different unrelat ed patients and in 6 of 92 control samples. The latter probably represents a benign polymorphism.