Cybulski Cezary, Wokołorczyk Dominika, Huzarski Tomasz, Byrski Tomasz, Gronwald Jacek, Górski Bohdan, Debniak Tadeusz, Masojć Bartłomiej, Jakubowska Anna, van de Wetering Thierry, Narod Steven A, Lubiński Jan
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Połabska 4, 70-115 Szczecin, Poland.
Breast Cancer Res Treat. 2007 Mar;102(1):119-22. doi: 10.1007/s10549-006-9320-y. Epub 2006 Aug 8.
To investigate the contribution of a founder deletion in the CHEK2 gene to the burden of breast cancer in Poland we studied 4,454 women with breast cancer and 5,496 population controls. Cases and controls were genotyped for the presence of a 5,395 bp founder deletion that removes exons 9 and 10 of the CHEK2 gene. This deletion has recently been described in a Czech and Slovak population. The cases and controls had previously been tested for two protein-truncating (IVS2 + 1G > A and 1100delC) and one missense CHEK2 mutation (I157T) which are characteristic for the population. The exons 9 and 10 deletion was present in 0.4% of the controls, in 1.0% (19 of 1,978) of unselected breast cancer cases (OR=2.2; 95% CI: 1.2-4.0; p = 0.01) and in 0.9% (28 of 3,228) of the early-onset cases (OR=2.0; 95% CI: 1.3-1.8; p = 0.02). One of the three truncating CHEK2 mutations (del5395; 1100delC or IVS2 + 1G > A) was seen in 101 of 4,454 (2.3%) cases and in 58 of 5,496 controls (1.1%) (OR=2.2; 95% CI: 1.6-3.0 p < 0.0001). A 5,395 bp founder deletion contributes to the burden of breast cancer in Poland. The deletion was present in 0.9% of the women with breast cancer diagnosed under the age of 51 and in 0.9% of women with breast cancer over the age of 50. This is one of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of all breast cancers in Poland can be attributed to one of three protein-truncating mutations in CHEK2.
为研究CHEK2基因中一种始祖缺失对波兰乳腺癌负担的影响，我们对4454例乳腺癌女性患者和5496例人群对照进行了研究。对病例组和对照组进行基因分型，检测是否存在一个5395 bp的始祖缺失，该缺失会导致CHEK2基因的外显子9和10缺失。这种缺失最近在捷克和斯洛伐克人群中被描述过。病例组和对照组之前已检测过两种导致蛋白质截短的CHEK2突变（IVS2 + 1G > A和1100delC）以及一种错义CHEK2突变（I157T），这些突变是该人群的特征性突变。外显子9和10缺失在0.4%的对照组、1.0%（1978例中19例）的未选择乳腺癌病例（比值比[OR]=2.2；95%置信区间[CI]：1.2 - 4.0；p = 0.01）以及0.9%（3228例中28例）的早发病例中出现（OR=2.0；95% CI：1.3 - 1.8；p = 0.02）。4454例病例中有101例（2.3%）以及5496例对照中有58例（1.1%）出现了三种导致蛋白质截短的CHEK2突变之一（del5395；1100delC或IVS2 + 1G > A）（OR=2.2；95% CI：1.6 - 3.0；p < 0.0001）。一个5395 bp的始祖缺失对波兰的乳腺癌负担有影响。该缺失在51岁以下诊断为乳腺癌的女性中占0.9%，在50岁以上乳腺癌女性中也占0.9%。这是波兰最常见的导致蛋白质截短的CHEK2变异之一。总体而言，波兰所有乳腺癌中有2%可归因于CHEK2的三种导致蛋白质截短的突变之一。
