Fu Guangbo, Tang Jialin, Wang Meilin, Qin Chao, Yan Fu, Ding Qi, Yin Changjun, Wang Xinru, Zhang Zhengdong
Key Laboratory of Reproductive Medicine, School of Public Health, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 210029, China ; Department of Urology, Huai-An First Affiliated Hospital, Nanjing Medical University, Huai-An, Jiangsu 211000, China.
J Biomed Res. 2011 Mar;25(2):128-34. doi: 10.1016/S1674-8301(11)60016-X.
Caspase-8 (CASP8) plays a key role in apoptosis. We examined by genotyping whether the -652 six-nucleotide insertion-deletion (6N ins/del) polymorphism in the CASP8 promoter region was associated with prostate cancer risk in a hospital-based case-control study of 406 Chinese prostate cancer patients and 408 age-matched cancer-free controls. Additionally, 23 prostate cancer tissues were analyzed for CASP8 mRNA expression. We found a significantly decreased prostate cancer risk for the 6N ins/del genotype [adjusted odds ratio (OR)=0.68; 95% confidence interval (CI)=0.51-0.92] and del/del genotype (OR=0.34; 95% CI=0.19-0.63) compared with the ins/ins genotype. The 6N del allele was associated dose-dependently with decreased prostate cancer risk (P trend = 0.001). RT-PCR showed that individuals with the 6N del allele had lower CASP8 mRNA levels than those with the ins/ins genotype (P = 0.024). These findings suggested that the CASP8-652 6N ins/del polymorphism may affect the susceptibility to prostate cancer and reduce prostate cancer risk among Chinese men.
半胱天冬酶8(CASP8)在细胞凋亡中起关键作用。在一项基于医院的病例对照研究中,我们对406例中国前列腺癌患者和408例年龄匹配的无癌对照进行基因分型,以检测CASP8启动子区域-652六核苷酸插入/缺失(6N ins/del)多态性是否与前列腺癌风险相关。此外,对23例前列腺癌组织进行了CASP8 mRNA表达分析。我们发现,与ins/ins基因型相比,6N ins/del基因型[校正比值比(OR)=0.68;95%置信区间(CI)=0.51-0.92]和del/del基因型(OR=0.34;95%CI=0.19-0.63)的前列腺癌风险显著降低。6N del等位基因与前列腺癌风险降低呈剂量依赖性相关(P趋势=0.001)。逆转录聚合酶链反应显示,携带6N del等位基因的个体的CASP8 mRNA水平低于携带ins/ins基因型的个体(P=0.024)。这些发现表明,CASP8-652 6N ins/del多态性可能影响中国男性对前列腺癌的易感性并降低前列腺癌风险。