Seppälä E H, Ikonen T, Mononen N, Autio V, Rökman A, Matikainen M P, Tammela T L J, Schleutker J
Laboratory of Cancer Genetics, Institute of Medical Technology, Lenkkeilijänkatu 8,University of Tampere and Tampere University Hospital, FIN-33014 University of Tampere, Finland.
Br J Cancer. 2003 Nov 17;89(10):1966-70. doi: 10.1038/sj.bjc.6601425.
Recently, variants in CHEK2 gene were shown to associate with sporadic prostate cancer in the USA. In the present study from Finland, we found that the frequency of 1100delC, a truncating variant that abrogates the kinase activity, was significantly elevated among 120 patients with hereditary prostate cancer (HPC) (four out of 120 (3.3%); odds ratio 8.24; 95% confidence interval 1.49-45.54; P=0.02) compared to 480 population controls. Suggestive evidence of segregation between the 1100delC mutation and prostate cancer was seen in all positive families. In addition, I157T variant had significantly higher frequency among HPC patients (13 out of 120 (10.8%); odds ratio 2.12; 95% confidence interval 1.06-4.27; P=0.04) than the frequency 5.4% seen in the population controls. The results suggest that CHEK2 variants are low-penetrance prostate cancer predisposition alleles that contribute significantly to familial clustering of prostate cancer at the population level.
最近，在美国，CHEK2基因变异被证明与散发性前列腺癌有关。在芬兰开展的本研究中，我们发现，在120例遗传性前列腺癌（HPC）患者中，一种可消除激酶活性的截短变异体1100delC的频率显著升高（120例中有4例（3.3%）；优势比8.24；95%置信区间1.49 - 45.54；P = 0.02），而在480名人群对照中该变异体频率较低。在所有阳性家族中均发现了1100delC突变与前列腺癌之间存在分离的提示性证据。此外，I157T变异体在HPC患者中的频率（120例中有13例（10.8%）；优势比2.12；95%置信区间1.06 - 4.27；P = 0.04）显著高于人群对照中的频率5.4%。结果表明，CHEK2变异体是低外显率的前列腺癌易感等位基因，在人群水平上对前列腺癌的家族聚集有显著贡献。
