MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.
MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.
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DOI：
10.1371/journal.pone.0128617
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vaughan TL
中科院分区：
文献类型：
--
作者：
Buas MF;Onstad L;Levine DM;Risch HA;Chow WH;Liu G;Fitzgerald RC;Bernstein L;Ye W;Bird NC;Romero Y;Casson AG;Corley DA;Shaheen NJ;Wu AH;Gammon MD;Reid BJ;Hardie LJ;Peters U;Whiteman DC;Vaughan TL
近几十年来，食管腺癌（EA）的发病率显著增加。EA及其前体巴雷特食管（BE）的多种危险因素已被确定，如反流、欧洲血统、男性、肥胖和吸烟，以及几种种系遗传变异最近与疾病风险相关。利用巴雷特和食管腺癌协会（BEACON）全基因组关联研究（GWAS）的数据，研究人员研究了2515例EA病例、3295例BE病例和3207例对照患者的单核苷酸多态性（snp），这些多态性可能影响microRNAs （miRNAs）的生物发生或生物活性，这些小的非编码rna参与转录后基因调控，并在许多癌症中不受调控。研究人员检测了三类基因的多态性与EA或BE风险的相关性：miRNA生物发生基因（157个snp， 21个基因）；miRNA基因位点（234个snp， 210个基因）；和mirna靶向mrna（177个snp， 158个基因）。29个snp与EA风险相关（P<0.05）， 25个snp与BE风险相关（P<0.05）。经过多次比较校正（FDR q>0.50）后，没有发现显著性差异，并且我们没有发现分析的变异与EA/BE的两个危险因素（吸烟和肥胖）之间相互作用的证据。该分析提供了迄今为止最广泛的与EA和BE风险相关的mirna相关snp评估。虽然miRNA生物发生核心通路中常见的遗传变异似乎不太可能调节EA或BE的易感性，但有必要进一步研究未评估的miRNA基因变异与疾病风险靶点之间的潜在关联。
Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P<0.05) of 29 SNPs with EA risk, and 25 SNPs with BE risk, were observed. None remained significant after correction for multiple comparisons (FDR q>0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.
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