Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort

Breast Cancer Res Treat. 2010 May;121(1):203-10. doi: 10.1007/s10549-009-0540-9. Epub 2009 Sep 18.


It has been proposed that rare variants within the double strand break repair genes CHEK2, BRIP1 and PALB2 predispose to breast cancer. The aim of this study was to evaluate the prevalence of these variants in an Irish breast cancer cohort and determine their contribution to the development of breast cancer in the west of Ireland. We evaluated the presence of CHEK2_1100delC variant in 903 breast cancer cases and 1,016 controls. Six previously described variants within BRIP1 and five within PALB2 were screened in 192 patients with early-onset or familial breast cancer. Where a variant was evident, it was then examined in the remainder of our 711 unselected breast cancer cases. CHEK2_1100delC was found in 5/903 (0.5%) breast cancer cases compared to 1/1016 (0.1%) controls. One mutation at BRIP1 (2392 C>T) was identified in the early-onset/familial cohort. Examination of this variant in the remainder of our cohort (711 cases) failed to identify any additional cases. None of the previously described PALB2 variants were demonstrated in the early-onset/familial cohort. We show evidence of CHEK2_1100delC and BRIP1 2392 C>T within the Irish population. CHEK2_1100delC and BRIP1 mutations incidence in Ireland is similar to that found in other unselected breast cancer cohorts from northern European countries. We found no evidence to suggest that PALB2 mutation is an important breast cancer predisposition gene in this population.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Checkpoint Kinase 2
  • Cohort Studies
  • DNA-Binding Proteins / genetics*
  • Fanconi Anemia Complementation Group N Protein
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Ireland
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics*
  • RNA Helicases / genetics*
  • Tumor Suppressor Proteins / genetics*


  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group N Protein
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Proteins
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases
  • BRIP1 protein, human
  • RNA Helicases