CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours

Br J Cancer. 2002 Dec 2;87(12):1445-8. doi: 10.1038/sj.bjc.6600637.


We have recently shown that the CHEK2*1100delC mutation acts as a low penetrance breast cancer susceptibility allele. To investigate if other CHEK2 variants confer an increased risk of breast cancer, we have screened an affected individual with breast cancer from 68 breast cancer families. Five of these individuals were found to harbour germline variants in CHEK2. Three carried the 1100delC variant (4%). One of these three individuals also carried the missense variant, Arg180His. In the other two individuals, missense variants, Arg117Gly and Arg137Gln, were identified. These two missense variants reside within the Forkhead-associated domain of CHEK2, which is important for the function of the expressed protein. None of these missense variants were present in 300 healthy controls. Microdissected tumours with a germline mutation showed loss of the mutant allele suggesting a mechanism for tumorigenesis other than a loss of the wild type allele. This study provides further evidence that sequence variation in CHEK2 is associated with an increased risk of breast cancer, and implies that tumorigenesis in association with CHEK2 mutations does not involve loss of the wild type allele.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Checkpoint Kinase 2
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genes, Tumor Suppressor*
  • Genetic Predisposition to Disease*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mutation
  • Pedigree
  • Polymerase Chain Reaction
  • Protein Kinases / genetics*
  • Protein-Serine-Threonine Kinases*
  • Risk Factors


  • Protein Kinases
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases