CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women

J Med Genet. 2011 Dec;48(12):860-3. doi: 10.1136/jmedgenet-2011-100380. Epub 2011 Nov 5.

Abstract

Background: Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors. This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk.

Methods and results: Homozygosity for the CHEK2*1100delC allele was identified in 8/2554 Dutch independent familial non-BRCA1/2 breast cancer cases. The genotype relative risk for breast cancer of homozygous and heterozygous familial breast cancer cases was 101.34 (95% CI 4.47 to 121 000) and 4.04 (95% CI 0.88 to 21.0), respectively. Female homozygotes appeared to have a greater than twofold increased breast cancer risk compared to familial CHEK2*1100delC heterozygotes (p=0.044). These results and the occurrence of multiple primary tumours in 7/10 homozygotes indicate a high cancer risk in homozygous women from non-BRCA1/2 families.

Conclusions: Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non-BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Checkpoint Kinase 2
  • Female
  • Frameshift Mutation*
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Heterozygote
  • Homozygote*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics*
  • Risk Factors

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases