Increased risk of breast cancer associated with CHEK2*1100delC.

PURPOSE

CHEK21100delC heterozygosity has been associated with increased risk of breast, prostate, and colorectal cancer in case-control studies. We tested the hypothesis that CHEK21100delC 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 CHEK21100delC 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 CHEK21100delC 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.