title: Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.
abstract: Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast cancer in low-resource settings.
authors: Center for Clinical Cancer  Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Jing
authors: J
authors: Zhang
authors: James D
authors: JD
authors: Fackenthal
authors: Yonglan
authors: Y
authors: Zheng
authors: Dezheng
authors: D
authors: Huo
authors: Ningqi
authors: N
authors: Hou
authors: Qun
authors: Q
authors: Niu
authors: Cecilia
authors: C
authors: Zvosec
authors: Temidayo O
authors: TO
authors: Ogundiran
authors: Anselm J
authors: AJ
authors: Hennis
authors: Maria Cristina
authors: MC
authors: Leske
authors: Barbara
authors: B
authors: Nemesure
authors: Suh-Yuh
authors: SY
authors: Wu
authors: Olufunmilayo I
authors: OI
authors: Olopade
mesh_terms: D000328:Adult; D001741:Black or African American; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001460:Barbados; D001483:Base Sequence; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D018095:Germ-Line Mutation; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009549:Nigeria
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human