Risk of Breast Cancer in Women With a CHEK2 Mutation With and Without a Family History of Breast Cancer
Risk of Breast Cancer in Women With a CHEK2 Mutation With and Without a Family History of Breast Cancer
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DOI：
10.1200/jco.2010.34.0778
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发表时间：
2011-10-01
影响因子：
45.3
通讯作者：
Lubinski, Jan
中科院分区：
文献类型：
--
作者：
Cybulski, Cezary;Wokolorczyk, Dominika;Lubinski, Jan
PurposeTo estimate the risk of breast cancer in a woman who has a CHEK 2 mutation depends on her family history of breast cancer.Patients and Methods 7494例BRCA 1突变阴性的乳腺癌患者和4,346例对照组女性进行CHEK 2基因4种创始突变的基因分型（del5395、IVS2 + 1G > A、1100delC和I157T）。（IVS 2 + 1G > A、1100 delC或del 5395）在227名患者（3.0%）和37名女性对照中存在（0.8%;比值比[OR]，3.6; 95%CI，2.6至5.1）。一级或二级亲属患有乳腺癌的女性的OR（OR，5.0; 95%CI，3.3至7.6）高于无家族史的女性（OR，3.3; 95%CI，2.3至4.7）。如果一级和二级亲属均患有乳腺癌，则OR为7.3（95%CI，3.2至16.8）。假设基线风险为6%，我们估计CHEK 2截短突变携带者的终生风险为20%，对于没有受影响亲属的女性，28%对于有一个二级亲属受影响的女性，34%对于有一个一级亲属受影响的女性，而44%的女性同时拥有第一和第二个结论CHEK 2突变筛查可检测出具有临床意义的乳腺癌风险，应考虑在所有有CHEK 2家族史的女性中进行筛查。乳腺癌CHEK 2截短突变和乳腺癌家族史阳性的女性一生中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。J Clin Oncol 29：3747-3752. (C)2011年美国临床肿瘤学会
PurposeTo estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer.Patients and MethodsSeven 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).ResultsA 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.ConclusionCHEK2 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. J Clin Oncol 29: 3747-3752. (C) 2011 by American Society of Clinical Oncology