Meta-analysis of new genome-wide association studies of colorectal cancer risk.
Meta-analysis of new genome-wide association studies of colorectal cancer risk.
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DOI：
10.1007/s00439-011-1055-0
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发表时间：
2012-02
期刊：
影响因子：
5.3
通讯作者：
Casey G
中科院分区：
文献类型：
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作者：
Peters U;Hutter CM;Hsu L;Schumacher FR;Conti DV;Carlson CS;Edlund CK;Haile RW;Gallinger S;Zanke BW;Lemire M;Rangrej J;Vijayaraghavan R;Chan AT;Hazra A;Hunter DJ;Ma J;Fuchs CS;Giovannucci EL;Kraft P;Liu Y;Chen L;Jiao S;Makar KW;Taverna D;Gruber SB;Rennert G;Moreno V;Ulrich CM;Woods MO;Green RC;Parfrey PS;Prentice RL;Kooperberg C;Jackson RD;Lacroix AZ;Caan BJ;Hayes RB;Berndt SI;Chanock SJ;Schoen RE;Chang-Claude J;Hoffmeister M;Brenner H;Frank B;Bézieau S;Küry S;Slattery ML;Hopper JL;Jenkins MA;Le Marchand L;Lindor NM;Newcomb PA;Seminara D;Hudson TJ;Duggan DJ;Potter JD;Casey G
结直肠癌是发达国家癌症死亡的第二大原因。全基因组关联研究（GWAS）已成功鉴定出结直肠癌的新易感位点。为了跟进这些发现，并尝试识别新的结直肠癌易感位点，我们提出了结直肠癌全基因组关联研究 (GWAS) 的结果（2,906 例病例，3,416 对照），这些研究此前尚未发表主要关联性。具体来说，我们使用对数加法模型计算了每项研究的比值比 (OR) 和 95% 置信区间 (CI)。为了提高我们检测新的结直肠癌易感位点的能力，我们结合了各项研究的结果进行了荟萃分析。我们使用 10 项独立研究（8,161 例病例和 9,101 例对照）选择了统计学上最显着的单核苷酸多态性 (SNP) 进行复制。我们再次使用荟萃分析来总结单独复制研究的结果，以及 GWAS 和复制研究的组合分析。我们测量了先前在结直肠癌易感性位点中发现的 10 个 SNP，发现其中 8 个与结直肠癌相关（p 值范围：0.02 至 1.8 × 10−8）。当我们排除之前发表的关于这些 SNP 的研究时，在综合分析中，5 个 SNP 仍然显着，p<0.05。经过多次测试调整后，在复制研究中没有发现任何新的易感性位点具有显着性，并且从 GWAS 和复制的组合分析来看，没有一个达到全基因组显着性。我们在染色体位置 20p12 的 BMP2 区域观察到第二个独立 SNP 的轻微显着证据（rs4813802；复制 p 值 0.03；组合 p 值 7.3 × 10−5）。在 5p33.15 的一个区域（包括 TERT-CLPTM1L 基因的编码区域）中，已在 GWAS 中鉴定出与至少七种其他癌症的易感性相关，我们观察到与 rs2853668 存在轻微显着关联（复制 p 值 0.03；组合 p 值 1.9 × 10−4）。我们的研究表明，常见遗传变异对结直肠癌风险的影响具有复杂性。
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow-up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for genome-wide association studies (GWAS) of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using 10 independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured 10 SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p-value range: 0.02 to 1.8 × 10−8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p<0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p-value 0.03; combined p-value 7.3 × 10−5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p-value 0.03; combined p-value 1.9 × 10−4). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.
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