A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer
A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer
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DOI：
10.1136/jmg.2006.044974
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发表时间：
2006-11-01
影响因子：
4
通讯作者：
Lubinski, J.
中科院分区：
文献类型：
--
作者：
Cybulski, C.;Wokolorczyk, D.;Lubinski, J.
背景：Chek 2激酶基因（CHEK 2）的种系突变与一系列癌症类型相关。最近，一个大的缺失外显子9和10的CHEK 2被确定在几个无关的捷克或斯洛伐克起源的乳腺癌患者。这个创始人等位基因的地理和种族范围尚未determined.Participants和方法：我们分析了这种缺失的存在，以及其他三个CHEK 2创始人突变，在1864例前列腺癌患者和5496对照来自波兰。在来自普通人群的5496名对照中的24名（0.4%）中检测到缺失，并且是波兰患者中最常见的CHEK 2截短创始者等位基因。在1864名前列腺癌患者中的15名（0.8%）（OR 1.9; 95%CI 0.97至3.5; p = 0.09）和249名家族性前列腺癌患者中的4名（OR 3.7; 95%CI 1.3至10.8; p = 0.03）中鉴定出缺失。这些OR值与其他截短突变（IVS 2 + 1GRA，1100 delC）的OR值相似。结论：CHEK 2基因第9和第10外显子的大量缺失增加了波兰男性前列腺癌的风险。del 5395 founder缺失可能存在于其他斯拉夫人群中，包括乌克兰、白俄罗斯、俄罗斯、波罗的海和巴尔干半岛的国家。这将是有趣的，看看在何种程度上这种缺失是负责前列腺癌的负担在其他人群。
Background: Germline mutations in the Chek2 kinase gene ( CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined.Participants and methods: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland.Results: The deletion was detected in 24 of 5496 ( 0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 ( 0.8%) men with unselected prostate cancer ( OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer ( OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations ( IVS2+ 1GRA, 1100delC).Conclusion: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.