Comprehensive Evaluation of the Impact of 14 Genetic Variants on Colorectal Cancer Phenotype and Risk
Comprehensive Evaluation of the Impact of 14 Genetic Variants on Colorectal Cancer Phenotype and Risk
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DOI：
10.1093/aje/kwr285
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发表时间：
2012-01-01
影响因子：
5
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
--
作者：
Lubbe, Steven J.;Di Bernardo, Maria Chiara;Houlston, Richard S.
为了全面评估最近发现的1q41、3q26.2、8q23.3、8q24.21、10p14、11q23.1、12q13.13、14q22.2、15q13.3、16q22.1、18q21.1、19q13.11、20p12.3和20q13.33变异对结直肠癌风险和结直肠癌表型的影响，作者分析了1999-2007年间来自英国的8878例病例和6051名对照。在50924名病例的一级亲属中，从年龄、性别和日历的特定结直肠癌比率中列举了变异对家族性结直肠癌风险的影响。14个易感基因座中的每一个都独立地影响结直肠癌，其风险随着携带的风险等位基因数目的增加而增加(每等位基因的优势比=1.13；P=2.99×10(-58))，对于那些位于高五分之一以内的人，风险增加了2.3倍。在具有=22个风险等位基因的病例的一级亲属中，标化发病率比分别为1.76、2.08和2.25。虽然14个结直肠癌易感基因座对个体风险预测的判别属性较差(曲线下面积=0.58)，但它们可以区分具有不同结直肠癌风险的人群亚组。
To comprehensively evaluate the impact of recently identified colorectal cancer (CRC) variants at 1q41, 3q26.2, 8q23.3, 8q24.21, 10p14, 11q23.1, 12q13.13, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12.3, and 20q13.33 on risk and CRC phenotype, the authors analyzed 8,878 cases and 6,051 controls from the United Kingdom ascertained in 1999-2007. The impact of variants on the familial CRC risk was enumerated from age-, sex-, and calendar-specific CRC rates in the 50,924 first-degree relatives of cases. Each of the 14 susceptibility loci independently influences CRC with the risk increasing with increasing number of risk alleles carried (per allele odds ratio = 1.13; P = 2.99 x 10(-58)) and, for those within the upper quintile, there is a 2.3-fold increased risk. In first-degree relatives of cases with = 22 risk alleles, standardized incidence ratios were 1.76, 2.08, and 2.25, respectively. Although the discriminatory attributes of the 14 CRC susceptibility loci for individual risk prediction are poor (area under the curve = 0.58), they may allow subgroups of the population at different CRC risks to be distinguished.