Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America

Cancer Genet Cytogenet. 2010 Oct 15;202(2):136-40. doi: 10.1016/j.cancergencyto.2010.07.124.

Abstract

The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted.

Publication types

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

MeSH terms

  • Adult
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Checkpoint Kinase 2
  • Family
  • Female
  • Frameshift Mutation / genetics*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • North America / ethnology
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics*
  • Sequence Deletion / genetics*

Substances

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