Weischer Maren, Bojesen Stig Egil, Tybjaerg-Hansen Anne, Axelsson Christen Kirk, Nordestgaard Børge Grønne
Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark.
J Clin Oncol. 2007 Jan 1;25(1):57-63. doi: 10.1200/JCO.2005.05.5160. Epub 2006 Jul 31.
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.
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.
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.
CHEK2*1100delC heterozygosity is associated with a three-fold risk of breast cancer in women in the general population.
在病例对照研究中，CHEK21100delC杂合性与乳腺癌、前列腺癌和结直肠癌风险增加相关。我们检验了这样一个假设，即普通人群中的CHEK21100delC杂合性会增加总体患癌风险，尤其是乳腺癌、前列腺癌和结直肠癌风险。
我们对来自丹麦普通人群的9231名个体进行了一项前瞻性研究，观察期为34年，并开展了一项病例对照研究，其中包括1101例乳腺癌病例和4665名对照。
在普通人群中，0.5%为杂合子，99.5%为非携带者。在前瞻性研究中，CHEK21100delC杂合子与非携带者相比，经多因素调整后的所有癌症风险比为1.2（95%可信区间，0.7至2.1），乳腺癌为3.2（95%可信区间，1.0至9.9），前列腺癌为2.3（95%可信区间，0.6至9.5），结直肠癌为1.6（95%可信区间，0.4至6.5）。在病例对照研究中，CHEK21100delC杂合子与非携带者相比，年龄匹配的乳腺癌优势比为2.6（95%可信区间，1.3至5.4）。在接受激素替代疗法、体重指数为25kg/m2或更高的60岁以上女性中，CHEK2*1100delC杂合子患乳腺癌的绝对10年风险达24%。
CHEK2*1100delC杂合性与普通人群中女性患乳腺癌的三倍风险相关。
