A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer
A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer
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DOI：
10.1007/s10549-008-0189-9
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发表时间：
2009-11-01
影响因子：
3.8
通讯作者：
Doerk, Thilo
中科院分区：
文献类型：
--
作者：
Bogdanova, Natalia;Cybulski, Cezary;Doerk, Thilo
共济失调-毛细血管扩张症(A-T)患者的血亲患乳腺癌的风险增加。等位基因的异质性使得确定ATM基因在普通人群中对乳腺癌易感性的作用变得困难。我们现在报告一种无义突变p.E1978X(C.5932G>；T)，在东欧人群中既是一种经典的A-T突变，也是乳腺癌的易感等位基因。在白俄罗斯的一项病例对照研究中，在1,891例白俄罗斯乳腺癌病例中发现了10例E1978X突变(0.5%)，而在1,019名对照人群中发现了1例E1978X突变[优势比(OR)：5.4；95%可信区间(95%CI)，0.7-42.4，P=0.1]。来自俄罗斯的第二项病例对照研究在611名乳腺癌患者中发现了两名俄罗斯人和一名乌克兰人的E1978X突变，但没有发现任何俄罗斯或乌克兰人的对照(P=0.1)。在来自波兰的第三项病例对照研究中，在7/3910例波兰乳腺癌患者中观察到了E1978X(0.2%)，而在2,010例非癌症对照人群中发现了1例(OR：3.6；95%CI：0.4-29.3，P=0.4)。在联合分析中，E1978X与乳腺癌显著相关(Mantel-Haenszel OR：5.6，95%CI：1.3-21.4，P=0.01)。综上所述，这项研究为东欧创始人群体中常见的A-T引起突变与乳腺癌的关联提供了第一个证据。
Blood relatives of patients with ataxia-telangiectasia (A-T) have an increased risk to develop breast cancer. Allelic heterogeneity has made it difficult to confirm the role of ATM, the gene mutated in A-T, for breast cancer susceptibility in the general population. We now report that a nonsense mutation, p.E1978X (c.5932G > T), is both a classical A-T mutation and a breast cancer susceptibility allele in Eastern European populations. In a case-control study from Belarus, the E1978X mutation was identified in 10/1,891 Byelorussian breast cancer cases (0.5%) compared with 1/1,019 population controls [odds ratio (OR): 5.4; 95% confidence interval (95% CI), 0.7-42.4, P = 0.1]. A second case-control study from Russia identified the E1978X mutation in two Russian and one Ukrainian cases out of 611 breast cancer patients but not in any Russian or Ukrainian controls (P = 0.1). In a third case-control study from Poland, E1978X was observed in 7/3,910 Polish breast cancer cases (0.2%) compared with 1/2,010 cancer-free population controls (OR: 3.6; 95% CI: 0.4-29.3, P = 0.4). In the combined analysis, E1978X was significantly associated with breast cancer (Mantel-Haenszel OR: 5.6, 95% CI: 1.3-21.4, P = 0.01). Taken together, this study provides first evidence for the association of a common A-T causing mutation with breast cancer in Eastern European founder populations.