Cybulski Cezary, Huzarski Tomasz, Górski Bohdan, Masojć Bartłomiej, Mierzejewski Marek, Debniak Tadeusz, Gliniewicz Bartłomiej, Matyjasik Joanna, Złowocka Elzbieta, Kurzawski Grzegorz, Sikorski Andrzej, Posmyk Michał, Szwiec Marek, Czajka Ryszard, Narod Steven A, Lubiński Jan
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Cancer Res. 2004 Apr 15;64(8):2677-9. doi: 10.1158/0008-5472.can-04-0341.
Variants in the CHEK2 have been found to be associated with prostate cancer risk in the United States and Finland. We sequenced CHEK2 gene in 140 Polish patients with prostate cancer and then genotyped the three detected variants in a larger series of prostate cancer cases and controls. CHEK2 truncating mutations (IVS2 + 1G>A or 1100delC) were identified in 9 of 1921 controls (0.5%) and in 11 of 690 (1.6%) unselected patients with prostate cancer [odds ratio (OR) = 3.4; P = 0.004]. These mutations were found in 4 of 98 familial prostate cases (OR = 9.0; P = 0.0002). The missense variant I157T was also more frequent in men with prostate cancer (7.8%) than in controls (4.8%), but the relative risk was more modest (OR = 1.7; P = 0.03). I157T was identified in 16% of men with familial prostate cancer (OR = 3.8; P = 0.00002). Loss of the wild-type CHEK2 allele was not observed in any of prostate cancers from five men who carried CHEK2-truncating mutations. Our results provide evidence that the two truncating mutations of CHEK2 confer a moderate risk of prostate cancer in Polish men and that the missense change appears to confer a modest risk.
在美国和芬兰，已发现CHEK2基因变异与前列腺癌风险相关。我们对140名波兰前列腺癌患者的CHEK2基因进行了测序，然后在更多的前列腺癌病例和对照中对检测到的三种变异进行了基因分型。在1921名对照中有9名（0.5%）以及在690名未经选择的前列腺癌患者中有11名（1.6%）鉴定出CHEK2截短突变（IVS2 + 1G>A或1100delC）[比值比（OR）= 3.4；P = 0.004]。在98例家族性前列腺癌病例中有4例发现了这些突变（OR = 9.0；P = 0.0002）。错义变异I157T在前列腺癌男性中（7.8%）也比在对照中（4.8%）更常见，但相对风险较小（OR = 1.7；P = 0.03）。在16%的家族性前列腺癌男性中鉴定出I157T（OR = 3.8；P = 0.00002）。在携带CHEK2截短突变的5名男性的任何前列腺癌中均未观察到野生型CHEK2等位基因缺失。我们的结果提供了证据，表明CHEK2的两种截短突变在波兰男性中赋予了中度前列腺癌风险，并且错义改变似乎赋予了适度风险。
