Originally published as JCO Early Release 10.1200/JCO.2007.12.5922 on January 2 2008

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CHEK2*1100delC Genotyping for Clinical Assessment of Breast Cancer Risk: Meta-Analyses of 26,000 Patient Cases and 27,000 Controls

Maren Weischer, Stig Egil Bojesen, Christina Ellervik, Anne Tybjærg-Hansen, Børge Grønne Nordestgaard

From the Department of Clinical Biochemistry, Herlev University Hospital; and the Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Denmark

Corresponding author: Børge Grønne Nordestgaard, MD, DMSc, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark DK-2730; e-mail: brno{at}heh.regionh.dk

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.

published online ahead of print at www.jco.org on January 2, 2008.

Supported by the Danish Medical Research Council and by the Copenhagen County Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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• Time to Check CHEK2 in Families With Breast Cancer?
  Kenneth Offit and Judy Ellen Garber
  JCO 2008 26: 519-520 [Full Text]

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• CHEK2*1100delC Screening of Asian Women With a Family History of Breast Cancer Is Unwarranted
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