Linkage disequilibrium mapping of CHEK2:: Common variation and breast cancer risk
Linkage disequilibrium mapping of CHEK2:: Common variation and breast cancer risk
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DOI：
10.1371/journal.pmed.0030168
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发表时间：
2006-06-01
期刊：
影响因子：
15.8
通讯作者：
Wedren, Sara
中科院分区：
文献类型：
--
作者：
Einarsdottir, Kristjana;Humphreys, Keith;Wedren, Sara
背景检测点蛋白2(Checkpoint kinase2，CHEK2)通过促进细胞周期停滞和激活基因损伤细胞的DNA修复来避免癌症的发生。以前的研究已经确定了CHEK2基因在乳腺癌病因学中的作用，但研究在很大程度上局限于罕见的1100delC突变。目前尚不清楚该基因的常见多态是否会影响患乳腺癌的风险。在这项研究中，我们旨在通过使用单倍型标签单核苷酸多态(Tag SNPs)捕获该基因的大部分多样性来评估常见的CHEK2变异对乳腺癌人群风险的重要性。方法和发现我们分析了92名瑞典女性CHEK2基因的14个常见SNPs，这些SNP覆盖了CHEK2基因52kb。覆盖率评估表明，这些类型的SNP也可以有效地传递来自同一区域的非类型SNP的关联信号。14个SNP中有6个能够很好地预测CHEK2中的单倍型和单SNP变异。我们在1,577例绝经后乳腺癌患者和1,513名对照人群中对这6个标签SNP进行了基因分型，但没有发现任何常见的CHEK2单倍型与乳腺癌风险之间令人信服的关联。1100delC突变在我们的瑞典人群中很少见--病例组为0.7%，对照组为0.4%，携带者与非携带者的相对优势比为2.26(95%可信区间，0.99-5.15)。人群频率和1100delC的优势比估计表明，我们的样本代表了北欧人群。结论尽管CHEK2基因与乳腺癌病因有关，但常见的多态并不影响绝经后乳腺癌的风险。
BackgroundCheckpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs).Methods and FindingsWe analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population - 0.7% in cases and 0.4% in controls with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99 - 5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population.ConclusionsNotwithstanding the involvement of the CHEK2 gene in breast cancer aetiology, we show that common polymorphisms do not influence postmenopausal breast cancer risk.