title: Inherited BRCA2 mutations in African Americans with breast and/or ovarian cancer: a study of familial and early onset cases.
abstract: In order to identify the spectrum of BRCA2 mutations in African Americans, breast or ovarian cancer patients from 74 independent families at elevated risk of germline mutations were investigated. The entire coding regions and flanking introns of BRCA2 were screened for germline mutations by single-stranded conformation polymorphism, protein truncation test, or denaturing high performance liquid chromatography followed by DNA sequencing. Eight distinct protein-truncating mutations were detected in six female patients (average age of onset of breast cancer: 37.6 years) and two male patients, but not in 163 unrelated disease-free controls. Two (1993delAA, 8643delAT) of the eight pathogenic mutations observed in African Americans have not been previously described. The other six pathogenic mutations (1882delT, 1991delATAA, 2001delTTAT, 2816insA, 4075delGT, 4088delA) have been detected in Caucasians; only the 2816insA mutation has been reported previously in African Americans. There were no significant differences in the frequency of deleterious BRCA2 mutations in African Americans compared with Caucasians. Six rare variations, not previously reported, were identified in five breast cancer patients but not in 163 disease-free control subjects. Of 11 different polymorphisms identified in high-risk African-American breast cancer patients, four may be unique to African Americans. An intron 10 polymorphism observed in patients was not detected in 163 disease-free African-American control subjects; this difference is statistically significant. Since many different pathogenic mutations and variants of unknown significance are observed in African Americans, BRCA2 genetic testing in high-risk African-American families must include the entire coding and flanking non-coding regions of the gene.
authors.affiliation: Department of Microbiology, Howard University College of Medicine and Cancer Center, Washington DC, USA.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Kanaan
authors.forename: Elikem
authors.initials: E
authors.lastname: Kpenu
authors.forename: Kim
authors.initials: K
authors.lastname: Utley
authors.forename: Lucile
authors.initials: L
authors.lastname: Adams-Campbell
authors.forename: Georgia M
authors.initials: GM
authors.lastname: Dunston
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.forename: Carolyn
authors.initials: C
authors.lastname: Broome
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D024682:BRCA2 Protein / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion; D014481:United States / Q000453:epidemiology; D001741:Black or African American
chemical_list: D024682:BRCA2 Protein