Originally published as JCO Early Release 10.1200/JCO.2005.05.5160 on July 31 2006

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Increased Risk of Breast Cancer Associated With CHEK2*1100delC

Maren Weischer, Stig Egil Bojesen, Anne Tybjærg-Hansen, Christen Kirk Axelsson, Børge Grønne Nordestgaard

From the Department of Clinical Biochemistry, Herlev University Hospital; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital; The Copenhagen City Heart Study, Bispebjerg University Hospital; and Department of Breast Surgery, Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark

Address reprint requests to Børge G. Nordestgaard, Professor and Chief Physician, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; e-mail: brno{at}herlevhosp.kbhamt.dk

Purpose CHEK2*1100delC heterozygosity has been associated with increased risk of breast, prostate, and colorectal cancer in case-control studies. We tested the hypothesis that CHEK2*1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorectal cancer in particular.

Patients and Methods We performed a prospective study of 9,231 individuals from the Danish general population, who were observed for 34 years, and we performed a case-control study including 1,101 cases of breast cancer and 4,665 controls.

Results Of the general population, 0.5% were heterozygotes and 99.5% were noncarriers. In the prospective study, multifactorially adjusted hazard ratios by CHEK2*1100delC heterozygosity versus noncarriers were 1.2 (95% CI, 0.7 to 2.1) for all cancers, 3.2 (95% CI, 1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6 (95% CI, 0.4 to 6.5) for colorectal cancer. In the case-control study, age-matched odds ratio for breast cancer by CHEK2*1100delC heterozygosity versus noncarriers was 2.6 (95% CI, 1.3 to 5.4). The absolute 10-year risk of breast cancer in CHEK2*1100delC heterozygotes amounted to 24% in women older than 60 years undergoing hormone replacement therapy, with a body mass index of 25 kg/m² or higher.

Conclusion CHEK2*1100delC heterozygosity is associated with a three-fold risk of breast cancer in women in the general population.

published online ahead of print at www.jco.org on July 31, 2006.

Supported by the Michaelsen Foundation, the Danish Heart Foundation, Chief Physician Johan Boserup and Lise Boserups Fund, the Danish Medical Research Council, the Research Fund at Rigshospitalet, Copenhagen University Hospital, and Copenhagen County.

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

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