Cybulski C, Wokołorczyk D, Huzarski T, Byrski T, Gronwald J, Górski B, Debniak T, Masojć B, Jakubowska A, Gliniewicz B, Sikorski A, Stawicka M, Godlewski D, Kwias Z, Antczak A, Krajka K, Lauer W, Sosnowski M, Sikorska-Radek P, Bar K, Klijer R, Zdrojowy R, Małkiewicz B, Borkowski A, Borkowski T, Szwiec M, Narod S A, Lubiński J
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul Połabska 4, 70-115 Szczecin, Poland.
J Med Genet. 2006 Nov;43(11):863-6. doi: 10.1136/jmg.2006.044974.
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.
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.
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+1G-->A, 1100delC).
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.
细胞周期检测点激酶2基因（CHEK2）的种系突变与多种癌症类型相关。最近，在几名捷克或斯洛伐克裔的无关乳腺癌患者中发现了CHEK2基因第9和10外显子的大片段缺失。这种奠基者等位基因的地理和种族范围尚未确定。
我们在1864例前列腺癌患者和5496例来自波兰的对照中检测了这种缺失以及其他三种CHEK2奠基者突变的存在情况。
在5496名普通人群对照中有24名（0.4%）检测到该缺失，它是波兰患者中最常见的CHEK2截短型奠基者等位基因。在1864名未经选择的前列腺癌男性中有15名（0.8%）检测到该缺失（比值比1.9；95%可信区间0.97至3.5；p = 0.09），在249名家族性前列腺癌男性中有4名（比值比3.7；95%可信区间1.3至10.8；p = 0.03）检测到该缺失。这些比值比与其他截短突变（IVS2+1G→A，1100delC）相关的比值比相似。
CHEK2基因第9和10外显子的大片段缺失使波兰男性患前列腺癌的风险增加。del5395奠基者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、波罗的海和巴尔干国家。看看这种缺失在多大程度上导致其他人群的前列腺癌负担将会很有意思。
