Characterization of Gene-Environment Interactions for Colorectal Cancer Susceptibility Loci
Characterization of Gene-Environment Interactions for Colorectal Cancer Susceptibility Loci
复制标题
DOI：
10.1158/0008-5472.can-11-4067
复制
发表时间：
2012-04-15
期刊：
影响因子：
11.2
通讯作者：
Peters, Ulrike
中科院分区：
文献类型：
--
作者：
Hutter, Carolyn M.;Chang-Claude, Jenny;Peters, Ulrike
全基因组关联研究已经确定了十几个与结直肠癌(CRC)风险相关的基因座。在这里，我们从9个队列和病例对照研究中检测了7,016例CRC病例和9,723例对照中10个这些基因座的单核苷酸多态(SNP)与可能的或已确定的环境危险因素之间的潜在影响-修饰。我们使用有效经验贝叶斯估计量的Meta分析来检测每个SNPs之间潜在的乘性相互作用[位于8q23.3的rs16892766(EIF3H/UTP23)，位于8q24的rs6983267(MYC)，位于10p14的rs10795668(FLJ3802842)，位于11q23的rs3802842(LOC120376)，位于14q22.2的rs4444235(BMP4)，位于15q13的rs4779584(GREM1)，位于16q22.1的rs9929218(CDH1)，位于18q21的rs4939827(Smad7)，位于19q13.1的rs10411210(RHPN2)，以及位于20p12.3的rs1253(RHP2)]，并选择主要的危险因素(体重指数、身高、吸烟状况、阿司匹林/抗炎药物的使用、炎症性药物的使用饮酒和饮食摄入钙、叶酸、红肉、加工肉类、蔬菜、水果和纤维)。在所有研究中，基因-环境交互作用的最有力的统计证据是蔬菜消费和rs16892766，位于染色体8q23.3上，靠近EIF3H和UTP23基因(标称P-交互作用=1.3 x 10(-4)；调整后的P=0.02)。SNP的主效应值随着蔬菜消费水平的增加而增大。在调整多次比较后，没有其他交互作用在统计上具有统计学意义。总体而言，在最初的GWAS中发现的大多数结直肠癌易感基因座的关联似乎与所考虑的其他危险因素不变；然而，我们的结果表明，食用蔬菜可能会改变rs16892766的影响。癌症资源；72(8)；2036-44。(C)2012年AACR。
Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P-interaction = 1.3 x 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. Cancer Res; 72(8); 2036-44. (C) 2012 AACR.