Novak David J, Sabbaghian Nelly, Maillet Philippe, Chappuis Pierre O, Foulkes William D, Tischkowitz Marc
Departments of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, QC, Canada H2W 1S6.
Breast Cancer Res Treat. 2009 Sep;117(2):453-9. doi: 10.1007/s10549-008-0134-y. Epub 2008 Aug 10.
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.
约半数的家族性乳腺癌病例是由在基因组稳定性维持中起关键作用的基因的种系突变引起的。参与DNA修复的相关基因突变可能是目前尚未明确病因的病例的原因。最近已确定两个这样的基因，RAP80和Abraxas，它们与BRCA1形成复合物，并且是BRCA1定位到DNA损伤位点所必需的。方法：在一个由95例具有不同种族背景的高危、非BRCA1/2乳腺癌病例组成的队列中筛查RAP80和Abraxas变体，这些病例包括德系犹太裔（n = 35）、加拿大混血（n = 34）和瑞士裔（n = 26）。结果：我们在RAP80中鉴定出四个错义变体、四个沉默单核苷酸多态性（SNP）、三个位于非翻译区（UTR）的SNP和七个内含子变体。对之前报道的两个RAP80变体进行了进一步研究。在Abraxas中，我们鉴定出两个错义变体、九个内含子变体和两个位于3'UTR的变体。结论：总体而言，RAP80或Abraxas的中度至高度显性等位基因似乎不太可能赋予显著高的乳腺癌相对风险。
