Relationship between 16 susceptibility loci and colorectal cancer phenotype in 3146 patients
Relationship between 16 susceptibility loci and colorectal cancer phenotype in 3146 patients
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DOI：
10.1093/carcin/bgr243
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发表时间：
2012-01-01
期刊：
影响因子：
4.7
通讯作者：
Houlston, Richard S.
中科院分区：
文献类型：
--
作者：
Lubbe, Steven J.;Whiffin, Nicola;Houlston, Richard S.
最近的全基因组关联研究发现了16个与结直肠癌风险相关的基因位点的单核苷酸多态性：rs6691170 （1q41）、rs10936599 （3q26.2）、rs16892766 （8q23.3）、rs6983267 （8q24.21）、rs10795668 （10p14）、rs3802842 （11q23.1）、rs11169552 （12q13.13）、rs4444235、rs1957636 （14q22.2）、rs4779584 （15q13.3）、rs9929218 （16q22.1）、rs4939827 （18q21.1）、rs10411210 （19q13.11）、rs961253和rs4813802 （20p12.3）和rs4925386 （20q13.33）。在本研究中，我们在3146例患者中检测了这些变异是否优先与肿瘤亚型（肿瘤部位、分期、分化程度和微卫星不稳定状态）相关。几个基因座与特定表型有统计学意义的关联，特别是与微卫星稳定性直肠疾病相关的rs6691170和rs3802842；Rs4779584、rs961253和rs4813802与微卫星稳定型结肠疾病相关，rs4444235和rs4925386与微卫星不稳定型结肠疾病相关。这些发现与基因座上的致病变异对不同形态发生途径的差异影响与结直肠癌发展中不同的病因危险因素一致。
Recent genome-wide association studies have identified single-nucleotide polymorphisms at 16 genetic loci associated with colorectal cancer risk: rs6691170 (1q41), rs10936599 (3q26.2), rs16892766 (8q23.3), rs6983267 (8q24.21), rs10795668 (10p14), rs3802842 (11q23.1), rs11169552 (12q13.13), rs4444235, rs1957636 (14q22.2), rs4779584 (15q13.3), rs9929218 (16q22.1), rs4939827 (18q21.1), rs10411210 (19q13.11), rs961253 and rs4813802 (20p12.3) and rs4925386 (20q13.33). In the present study, we examined whether these variants are preferentially associated with tumour subtype-tumour site, stage, degree of differentiation and microsatellite instability status-in 3146 patients. Several loci showed statistically significant associations with specific phenotypes notably rs6691170 and rs3802842 associated with microsatellite stable rectal disease; rs4779584, rs961253 and rs4813802 associated with microsatellite stable colonic disease and rs4444235 and rs4925386 with microsatellite instability colonic disease. These findings are consistent with pathogenic variants in loci differentially impacting on distinct morphogenetic pathways consistent with aetiologically different risk factors in the development of colorectal cancer.