CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls

J Clin Oncol. 2008 Feb 1;26(4):542-8. doi: 10.1200/JCO.2007.12.5922. Epub 2008 Jan 2.


Purpose: CHEK2*1100delC heterozygosity may be associated with an increased risk of breast cancer; however, it is unclear whether the evidence is sufficient to recommend genotyping in clinical practice.

Patients and methods: We identified studies on CHEK2*1100delC heterozygosity and the risk of unselected, early-onset, and familial breast cancer through comprehensive, computer-based searches of PubMed, EMBASE, and Web of Science. Aggregated risk estimates were compared with previous estimates for BRCA1 and BRCA2 mutation heterozygotes.

Results: By using fixed-effect models for CHEK2*1100delC heterozygotes versus noncarriers, we found aggregated odds ratios of 2.7 (95% CI, 2.1 to 3.4) for unselected breast cancer, 2.6 (95% CI, 1.3 to 5.5) for early-onset breast cancer, and 4.8 (95% CI, 3.3 to 7.2) for familial breast cancer. For familial breast cancer, this corresponds to a cumulative risk of breast cancer at age 70 years in CHEK2*1100delC heterozygotes of 37% (95% CI, 26% to 56%), which compares with similar previous estimates of 57% (95% CI, 47% to 66%) for BRCA1 mutation heterozygotes and 49% (95% CI, 40% to 57%) for BRCA2 mutation heterozygotes.

Conclusion: These meta-analyses emphasize that CHEK2*1100delC is an important breast cancer-predisposing gene, which increases the risk three- to five-fold. Because the cumulative risk of breast cancer at age 70 years among familial patient cases for CHEK2*1100delC heterozygotes is almost as high as that for BRCA1 and BRCA2 mutation heterozygotes, genotyping for CHEK2*1100delC should be considered together with BRCA1 and BRCA2 mutation screening in women with a family history of breast cancer.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Apoptosis Regulatory Proteins
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Checkpoint Kinase 2
  • Female
  • Genetic Carrier Screening*
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing*
  • Genotype
  • Humans
  • Mutation*
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk Assessment


  • Apoptosis Regulatory Proteins
  • BLID protein, human
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases