Background:
An overview of the state of genetic testing for brca1 and brca2 genes was presented at the summit meeting on breast cancer among african american women.
Methods:
An exhaustive literature search was performed using pubmed and abstracts published from meetings of the american association for cancer research, the american society of human genetics, and the american society of clinical oncology. the breast cancer information core was also searched for information regarding sequence variants in which the ethnicity of the individual tested was known.
Results:
Of the 26 distinct brca1 pathogenic mutations (protein-truncating, disease-associated missense, and splice variants) detected in africans or african americans, 15 (58%) have not been previously reported. in addition, 18 deleterious brca2 mutations have been identified and 10 (56%) of these are unique to the group. only two pathogenic brca1 mutations (943ins10 and m1775r) have been detected in three or more unrelated families. however, seven additional brca1 or brca2 deleterious mutations have been reported in at least two unrelated families. three of these recurrent brca1 mutations (943ins10, 1832del5, and 5296del4) have been characterized by haplotype studies and each likely arose from a common ancestor, including one ancestor that could be traced to the ivory coast in west africa. although only a few african-american families have been tested for brca1 and brca2 mutations, the probability of finding a mutation is invariably dependent on the age of onset and the number of breast and/or ovarian cancer cases in the family. the psychosocial implications of genetic testing for african americans have not been well studied, so that high-risk african americans may underestimate their risks of breast and ovarian cancer.
Conclusions:
Deleterious brca1 and brca2 mutations have been identified in african-american and african families. a number of unique mutations have been described, but recurrent mutations are widely dispersed and are not readily identifiable in the few families that have been tested. access to genetic counseling and testing in a culturally sensitive research setting must remain a high priority before genetic testing can be disseminated in the community.