A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3
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DOI：
10.1038/ng.111
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发表时间：
2008-05-01
期刊：
影响因子：
30.8
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
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作者：
Tomlinson, Ian P. M.;Webb, Emily;Houlston, Richard S.
为了确定结直肠癌（CRC）易感等位基因，我们进行了一项全基因组关联研究。在一期研究中，我们对940例家族性结直肠癌患者（627例结直肠癌，313例高危腺瘤）和965例对照患者进行了550163个标签snp基因分型。在第二阶段，我们在2873例CRC病例和2871例对照中选择了42708个snp进行基因分型。在3期研究中，我们在4287例CRC病例和3743例对照的1期和2期联合分析中评估了11个snp，显示P < 10（-4）的相关性。两个snp被用于4期基因分型（来自8个中心的10,731例CRC病例和10,961例对照）。除了先前报道的8q24、15q13和18q21 CRC风险位点外，我们还发现了两个先前未报道的关联：rs10795668，位于10p14 (P=2.5 x 10(-13))；P=6.9 x 10（-12）复制)，rs16892766为8q23.3 (P=3.3 x 10（-18）总体；P=9.6 x 10（-17）复制)，它标记了一个可能的致病基因EIF3H。这些数据为CRC易感性的“共病共变”模型提供了进一步的证据。
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping ( 10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P=2.5 x 10(-13) overall; P=6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P=3.3 x 10(-18) overall; P=9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.