Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24
Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24
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DOI：
10.1038/ng2089
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发表时间：
2007-08-01
期刊：
影响因子：
30.8
通讯作者：
Dunlop, Malcolm G.
中科院分区：
文献类型：
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作者：
Zanke, Brent W.;Greenwood, Celia M. T.;Dunlop, Malcolm G.
使用包括7,480名受影响个体和7,779名对照的多阶段遗传关联方法，我们确定了染色体区域8q24中与结直肠癌相关的标记。在第一阶段，我们对安大略省1,257名患者和1,336名对照的99,632个SNPs进行了基因分型。在阶段2-4中，我们对来自西雅图、纽芬兰和苏格兰的4,024名患者和4,042名对照进行了系列复制研究。我们在染色体8q24和9p24上分别发现1-4期的合并优势比(OR)分别为1.18(趋势；P=1.41×10(-8))和1.14(趋势；P=1.32×10(-5))。对来自法国和欧洲的2199名受影响个体和2401名对照进行的其他分析支持8q24基因座的关联(OR=1.16，趋势；95%可信区间：1.07-1.26；P=5.05=10-4)。对8q24基因座的所有7项研究的总结具有非常显著的意义(OR=1.17，C.I.：1.12-1.23；P=3.16 x 10(-11))。该基因座也与前列腺癌有关(1-3)。
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 = 10-4). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer(1-3).