Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian families with high risk of breast cancer

J Hum Genet. 2009 Mar;54(3):152-61. doi: 10.1038/jhg.2009.6. Epub 2009 Feb 6.


Breast cancer is a heterogeneous disease displaying some degree of familial clustering. Highly penetrant breast cancer susceptibility genes represent approximately 20-25% of the familial aggregation of breast cancer. A significant proportion of this familial aggregation of breast cancer is thus yet to be explained by other breast cancer susceptibility genes. Given the high susceptibility conferred by the two major breast cancer predisposition genes, BRCA1 and BRCA2 and the implication of these genes in many key cellular processes, assessment of genes encoding BRCA1-interacting proteins as plausible breast cancer candidate genes is thus attractive. In this study, four genes encoding BRCA1-interacting proteins were analyzed in a cohort of 96 breast cancer individuals from high-risk non-BRCA1/BRCA2 French Canadian families. Although no deleterious truncating germline mutations or aberrant spliced mRNA species were identified, a total of 10, 4, 11 and 6 variants were found in the AURKA, BAP1, BARD1 and DHX9 genes, respectively. The allele frequency of each variant was further ascertained in a cohort of 98 healthy French Canadian unrelated women and a difference in allele frequency was observed for one BARD1 variant based on single-marker analysis. Haplotype estimation, haplotype blocks and tagging SNPs identification were then performed for each gene, providing a valuable tool for further searches of common disease-associated variants in these genes and therefore further analyses on these genes in larger cohorts is warranted in the search of low-to-moderate penetrance breast cancer susceptibility alleles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A
  • Aurora Kinases
  • BRCA1 Protein / genetics*
  • Base Sequence
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Canada
  • Case-Control Studies
  • DEAD-box RNA Helicases / genetics
  • Family
  • Female
  • France / ethnology
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Haplotypes
  • Heterozygote
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Neoplasm Proteins / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Whites / genetics*


  • BAP1 protein, human
  • BRCA1 Protein
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • Ubiquitin Thiolesterase
  • DHX9 protein, human
  • DEAD-box RNA Helicases