Wang Yue, Dai Bo, Ye Dingwei
Department of Urology, Fudan University Shanghai Cancer Center Shanghai 20032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 20032, China.
Int J Clin Exp Med. 2015 Sep 15;8(9):15708-15. eCollection 2015.
CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed.
We performed a systematic review and meta-analysis to clarify the association between CHEK2 1100delC, IVS2+1G>A, I157T mutation and risk of Prostate Cancer. A comprehensive, computerized literature search of PubMed until December 27, 2014 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated using the fixed effects model or random effects model according to heterogeneity between studies.
Eight eligible studies were included in the analysis, all were retrospective studies. The overall meta-analysis demonstrated that the CHEK2 1100delC mutation (OR 3.29; 95% confidence interval: 1.85-5.85; P = 0.00) and I157T missense mutation (OR 1.80; 95% confidence interval: 1.51-2.14; P = 0.00) was associated with higher risk of Prostate Cancer, and CHEK2 1100delC mutation is irrelevant to familial aggregation phenomenon of prostate cancer (OR 1.59; 95% confidence interval: 0.79-3.20; P = 0.20). The IVS2+1G>A mutation is also irrelevant to Prostate Cancer (OR = 1.59, 95% CI = 0.93-2.71, P = 0.09). None of the single studies materially altered the original results and no evidence of publication bias was found.
CHEK2 1100delC mutation and I157T missense mutation in males indicates higher risk of Prostate Cancer, but there's no evidence to prove the CHEK2 1100delC mutation was associated with Familial prostate cancer.
CHEK2基因编码一种G2期检查点激酶,其在DNA修复过程中发挥关键作用。该基因突变会增加患乳腺癌的风险。也有人提出其会增加患前列腺癌的风险,但尚未得到证实。
我们进行了一项系统综述和荟萃分析,以阐明CHEK2基因1100delC、IVS2+1G>A、I157T突变与前列腺癌风险之间的关联。截至2014年12月27日,我们利用计算机对PubMed进行了全面的文献检索。根据特定的纳入标准纳入符合条件的研究。根据各研究间的异质性,使用固定效应模型或随机效应模型估计合并风险比。
八项符合条件的研究被纳入分析,均为回顾性研究。总体荟萃分析表明,CHEK2基因1100delC突变(比值比3.29;95%置信区间:1.85-5.85;P=0.00)和I157T错义突变(比值比1.80;95%置信区间:1.51-2.14;P=0.00)与前列腺癌的较高风险相关,而CHEK2基因1100delC突变与前列腺癌的家族聚集现象无关(比值比1.59;95%置信区间:0.79-3.20;P=0.20)。IVS2+1G>A突变也与前列腺癌无关(比值比=1.59,95%置信区间=0.93-2.71,P=0.09)。没有一项单独研究对原始结果产生重大影响,也未发现发表偏倚的证据。
男性中CHEK2基因1100delC突变和I157T错义突变表明患前列腺癌的风险较高,但没有证据证明CHEK2基因1100delC突变与家族性前列腺癌有关。