Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk.
Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk.
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DOI：
10.1158/1055-9965.epi-15-0596
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Wu AH
中科院分区：
文献类型：
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作者：
Lee E;Stram DO;Ek WE;Onstad LE;MacGregor S;Gharahkhani P;Ye W;Lagergren J;Shaheen NJ;Murray LJ;Hardie LJ;Gammon MD;Chow WH;Risch HA;Corley DA;Levine DM;Whiteman DC;Bernstein L;Bird NC;Vaughan TL;Wu AH
从全基因组关联研究（GWAS）中发现的几个癌症相关基因座与多种癌症部位的风险相关，表明多效性效应。我们调查了gwas识别的其他常见癌症的风险变异是否与食管腺癌（EA）或其前体巴雷特食管（BE）的风险相关。我们通过使用来自巴雷特和食管腺癌遗传易感性研究的2163名对照参与者和3885名（1501名EA和2384名BE）病例患者的基因型数据，研究了EA和BE风险与387个与其他癌症风险相关的单核苷酸多态性（snp）之间的关联，并调查了吸烟史、体重指数（BMI）和反流/胃灼热对效应的影响。经过多次检测校正后，387个snp与EA或BE的风险均无统计学意义相关。没有观察到吸烟、BMI或反流/胃灼热改变疗效的证据。从GWAS中发现的常见癌症的遗传风险变异似乎与EA或be的风险无关。据我们所知，这是对EA和BE风险的多效性遗传关联的首次调查。
Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus (BE). We examined the associations between risks of EA and BE and 387 single nucleotide polymorphisms (SNPs) that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 BE) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or BE. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or BE. To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and BE.