Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, , Chongqing, China.
Gut. 2014 Feb;63(2):326-36. doi: 10.1136/gutjnl-2012-304121. Epub 2013 Aug 14.
In the past two decades, approximately 1000 reports have been published regarding associations between genetic variants in candidate genes and risk of colorectal cancer (CRC). Study results are inconsistent. We aim to provide a synopsis of the current understanding of genetic factors for CRC risk through systematically evaluating results from previous studies.
We searched PubMed and Google Scholar to identify papers that investigated associations between genetic variants and CRC risk and published through 25 December 2012. With data from 950 papers, we conducted 910 meta-analyses for 267 genetic variants in 150 candidate genes with at least three data sources. We used Venice criteria and false-positive report probability tests to grade levels of cumulative epidemiological evidence of significant associations with CRC risk.
Sixty-two variants in 50 candidate genes showed a nominally significant association with CRC risk (p<0.05). Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (APC), CHEK2, DNMT3B, MLH1 and MUTYH), moderate for two variants in two genes (GSTM1 and TERT), and weak for 52 variants in 45 genes. Additionally, 40 variants in 33 genes showed convincing evidence of no association with CRC risk in meta-analyses including at least 5000 cases and 5000 controls.
Approximately 4% of genetic variants evaluated to date in candidate-gene association studies showed moderate to strong cumulative epidemiological evidence of an association with CRC risk. These genetic variants, if confirmed, may explain approximately 5% of familial CRC risk.
在过去的二十年中，约有 1000 份报告发表了候选基因中遗传变异与结直肠癌（CRC）风险之间的关联。研究结果不一致。我们旨在通过系统评估以往研究的结果，提供对 CRC 风险遗传因素的综合理解。
我们搜索了 PubMed 和 Google Scholar，以确定截至 2012 年 12 月 25 日调查遗传变异与 CRC 风险之间关联的论文。使用来自 950 篇论文的数据，我们对 150 个候选基因中的 267 个遗传变异进行了 910 次荟萃分析，这些基因至少有三个数据来源。我们使用威尼斯标准和假阳性报告概率检验来对与 CRC 风险显著相关的累积流行病学证据水平进行分级。
在 50 个候选基因中的 62 个变异与 CRC 风险具有名义上的显著关联（p<0.05）。与 CRC 风险具有显著关联的累积流行病学证据被评为强的有五个基因中的八个变异（APC、CHEK2、DNMT3B、MLH1 和 MUTYH），两个基因中的两个变异（GSTM1 和 TERT）为中度，45 个基因中的 52 个变异为弱。此外，在包括至少 5000 例病例和 5000 例对照的荟萃分析中，33 个基因中的 40 个变异显示出与 CRC 风险无关联的令人信服的证据。
迄今为止，在候选基因关联研究中评估的约 4%的遗传变异具有中度至强的累积流行病学证据表明与 CRC 风险相关。如果得到证实，这些遗传变异可能解释大约 5%的家族性 CRC 风险。
