Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility
Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility
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DOI：
10.1086/373965
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发表时间：
2003-04-01
影响因子：
9.8
通讯作者：
Rahman, N
中科院分区：
文献类型：
--
作者：
Schutte, M;Seal, S;Rahman, N
我们最近报道了细胞周期检查点激酶CHEK 2（CHEK 2 1100 delC）的序列变异是BRCA 1或BRCA 2突变非携带者中的低突变率乳腺癌易感性等位基因。为了研究其他CHEK 2变异是否赋予乳腺癌易感性，我们在来自89个具有三个或更多乳腺癌病例的家系的BRCA 1/2阴性乳腺癌病例中筛选了完整的CHEK 2编码序列。我们在两个不同的家族中发现了一种新的种系变异体R117 G。为了评估R117 G和其他地方报道的两种生殖系变异R145 W和I157 T与乳腺癌的可能关联，我们筛选了来自605个家庭的737例BRCA 1/2阴性家族性乳腺癌病例，来自335个家庭的459例BRCA 1/2阳性病例，以及来自英国、荷兰和北美的723例对照。所有这三种变异在所有组中都很罕见，与对照组相比，家族性乳腺癌病例中的发生频率都没有显著升高。这些结果表明，1100 delC可能是唯一的CHEK 2等位基因，使乳腺癌易感性的一个可观的贡献。
We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants reported elsewhere, R145W and I157T with breast cancer, we screened 737 BRCA1/2-negative familial breast cancer cases from 605 families, 459 BRCA1/2-positive cases from 335 families, and 723 controls from the United Kingdom, the Netherlands, and North America. All three variants were rare in all groups, and none occurred at significantly elevated frequency in familial breast cancer cases compared with controls. These results indicate that 1100delC may be the only CHEK2 allele that makes an appreciable contribution to breast cancer susceptibility.