title: Analysis of the genes coding for the BRCA1-interacting proteins, RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic breast cancer cases.
abstract: Background Around half of familial breast cancer cases are caused by germ-line mutations in genes which are critically involved in the maintenance of genome stability. Mutations in related genes functioning in DNA repair may account for currently unattributed cases. Two such genes, RAP80 and Abraxas, have recently been identified to be in a complex with BRCA1, and are required for the localization of BRCA1 to DNA damage foci. Methods RAP80 and Abraxas variants were screened for in a cohort of 95 high risk, non-BRCA1/2 breast cancer cases of varying ethnicity: those of Ashkenazi Jewish (n = 35), mixed Canadian (n = 34) and Swiss descent (n = 26). Results We have identified four missense variants, four silent SNPs, three SNPs in the UTRs and seven intronic variants in RAP80. Two of the previously reported RAP80 variants were further investigated. In Abraxas, we have identified two missense, nine intronic and two variants in the 3' UTR. Conclusions Overall, it seems unlikely that moderate to highly penetrant alleles of either RAP80 or Abraxas, confer a significantly high relative risk of breast cancer.
authors.affiliation: Departments of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, QC, Canada H2W 1S6.
authors.forename: David J
authors.initials: DJ
authors.lastname: Novak
authors.forename: Nelly
authors.initials: N
authors.lastname: Sabbaghian
authors.forename: Philippe
authors.initials: P
authors.lastname: Maillet
authors.forename: Pierre O
authors.initials: PO
authors.lastname: Chappuis
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Marc
authors.initials: M
authors.lastname: Tischkowitz
mesh_terms: D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D056488:Histone Chaperones; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors
chemical_list: C520310:ABRAXAS1 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; C466234:UIMC1 protein, human