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脂联素基因座的常见变异与英国人群的结直肠癌风险无关。

Common variation at the adiponectin locus is not associated with colorectal cancer risk in the UK.

作者信息

Carvajal-Carmona Luis G, Spain Sarah, Kerr David, Houlston Richard, Cazier Jean-Baptiste, Tomlinson Ian

机构信息

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

出版信息

Hum Mol Genet. 2009 May 15;18(10):1889-92. doi: 10.1093/hmg/ddp109. Epub 2009 Mar 5.

Abstract

A recent study examined common genetic variants at the adiponectin locus (ADIPOQ) in two case-control colorectal cancer (CRC) series from the USA and reported a positive association between a single nucleotide polymorphism (SNP) in the 5' region of the gene (rs266729) and decreased disease risk. In an attempt to replicate the previously reported association, we examined data from two CRC genome-wide association studies based on the UK population. The first cohort comprised 931 familial colorectal tumour cases and 929 cancer-free controls. The second included 1216 individuals with Dukes stage B or C CRCs from two clinical trials and 1436 controls from the 1958 Birth Cohort. We tested associations between CRC risk and 82 SNPs in a region of 250 kb around the ADIPOQ gene; nine of these SNPs were located in the coding and promoter regions. None of the markers tested was significantly associated with CRC risk after correction for multiple testing under any of the models in any of the two cohorts. A meta-analysis of the data also failed to detect any association. We, therefore, failed to replicate an association between common variants at ADIPOQ and CRC risk in the UK, and suggest that the previous report is either population-specific or a false-positive result.

摘要

最近一项研究在美国的两个病例对照结直肠癌(CRC)系列中检测了脂联素基因座(ADIPOQ)的常见基因变异,并报告该基因5'区域的一个单核苷酸多态性(SNP,rs266729)与疾病风险降低之间存在正相关。为了重复先前报道的相关性,我们研究了基于英国人群的两项CRC全基因组关联研究的数据。第一个队列包括931例家族性结直肠肿瘤病例和929例无癌对照。第二个队列包括来自两项临床试验的1216例Dukes B期或C期CRC患者以及来自1958年出生队列的1436例对照。我们测试了ADIPOQ基因周围250 kb区域内82个SNP与CRC风险之间的相关性;其中9个SNP位于编码区和启动子区。在两个队列中的任何一个队列中,经过任何模型下的多重检验校正后,所测试的标记物均与CRC风险无显著相关性。对数据进行的荟萃分析也未发现任何相关性。因此,我们未能在英国重复ADIPOQ常见变异与CRC风险之间的相关性,并认为先前的报告要么具有人群特异性,要么是假阳性结果。

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