International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul. Połabska 4, 70-115 Szczecin, Poland.
J Clin Oncol. 2011 Oct 1;29(28):3747-52. doi: 10.1200/JCO.2010.34.0778. Epub 2011 Aug 29.
To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer.
Seven thousand four hundred ninety-four BRCA1 mutation-negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T).
A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both a first- and second-degree relative affected.
CHEK2 mutation screening detects a clinically meaningful risk of breast cancer and should be considered in all women with a family history of breast cancer. Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.
根据乳腺癌家族史，评估携带 CHEK2 突变的女性罹患乳腺癌的风险。
对 7494 名 BRCA1 阴性乳腺癌患者和 4346 名对照女性进行 CHEK2 四个常见突变（del5395、IVS2+1G>A、1100delC 和 I157T）的基因分型。
227 名患者（3.0%）和 37 名女性对照（0.8%）存在截断突变（IVS2+1G>A、1100delC 或 del5395）（比值比 [OR]，3.6；95%置信区间 [CI]，2.6 至 5.1）。与无家族史的女性（OR，3.3；95%CI，2.3 至 4.7）相比，一级或二级亲属中有乳腺癌患者的女性风险更高（OR，5.0；95%CI，3.3 至 7.6）。如果一级和二级亲属均患有乳腺癌，OR 为 7.3（95%CI，3.2 至 16.8）。假设基线风险为 6%，我们估计携带 CHEK2 截断突变的女性终生罹患乳腺癌的风险为：无受影响亲属的女性为 20%，有一个二级亲属受影响的女性为 28%，有一个一级亲属受影响的女性为 34%，有一个一级亲属和一个二级亲属受影响的女性为 44%。
CHEK2 突变筛查可发现具有临床意义的乳腺癌风险，应考虑在所有有乳腺癌家族史的女性中进行。携带 CHEK2 截断突变且有乳腺癌阳性家族史的女性，终生罹患乳腺癌的风险大于 25%，是磁共振成像筛查和他莫昔芬化学预防的候选人群。
