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.
1.Departments of Oncology and Human Genetics, Program in Cancer GeneticsMcGill UniversityMontrealCanada
2.Departments of Medicine and Human GeneticsMcGill UniversityMontrealCanada
3.Segal Cancer CenterMcGill University Sir M. B. Davis-Jewish General HospitalMontrealCanada
4.Laboratory of Molecular Oncology, Division of Laboratory Medicine, Department of Genetic Medicine and LaboratoryUniversity Hospitals of GenevaGeneva 14Switzerland
5.Unit of Oncogenetics and Cancer Prevention, Division of Oncology, Department of Internal Medicine; Division of Genetic Medicine, Department of Genetic Medicine and Laboratory University Hospitals of GenevaGeneva 14Switzerland
6.The Research InstituteMcGill University Health CentreMontrealCanada