Department of Health Statistics, Army Medical University, Chongqing, China.
Medical Department, The 305 Hospital of Chinese People's Liberation Army, Beijing, China.
Cancer Epidemiol Biomarkers Prev. 2020 Apr;29(4):838-849. doi: 10.1158/1055-9965.EPI-19-1281. Epub 2020 Jan 22.
A large number of studies have been conducted to investigate associations between genetic variants and esophageal cancer risk in the past several decades. However, findings from these studies have been generally inconsistent. We aimed to provide a summary of the current understanding of the genetic architecture of esophageal cancer susceptibility.
We performed a comprehensive field synopsis and meta-analysis to evaluate associations between 95 variants in 70 genes or loci and esophageal cancer risk using data from 304 eligible publications, including 104,904 cases and 159,797 controls, through screening a total of 21,328 citations. We graded levels of cumulative epidemiologic evidence of a significant association with esophageal cancer using the Venice criteria and false-positive report probability tests. We constructed functional annotations for these variants using data from the Encyclopedia of DNA Elements Project and other databases.
Thirty variants were nominally significantly associated with esophageal cancer risk. Cumulative epidemiologic evidence of a significant association with overall esophageal cancer, esophageal squamous cell carcinoma, or esophageal adenocarcinoma was strong for 13 variants in or near 13 genes (, and ). Bioinformatics analysis suggested that these variants and others correlated with them might fall in putative functional regions.
Our study summarizes the current literature on the genetic architecture of esophageal cancer susceptibility and identifies several potential polymorphisms that could be involved in esophageal cancer susceptibility.
These findings provide direction for future studies to identify new genetic factors for esophageal cancer.
在过去几十年中，已经进行了大量研究来探讨遗传变异与食管癌风险之间的关联。然而，这些研究的结果通常不一致。我们旨在提供对食管癌易感性遗传结构的当前理解的总结。
我们通过筛选总共 21328 条引文，使用来自 304 篇合格出版物的数据（包括 104904 例病例和 159797 例对照），进行了全面的领域综述和荟萃分析，以评估 70 个基因或基因座中的 95 个变异与食管癌风险之间的关联。我们使用威尼斯标准和虚假阳性报告概率检验来评估与食管癌显著关联的累积流行病学证据水平。我们使用 DNA 元素百科全书项目和其他数据库的数据为这些变体构建功能注释。
30 个变体与食管癌风险有显著的名义关联。在 13 个基因或附近的 13 个变体中，整体食管癌、食管鳞状细胞癌或食管腺癌的累积流行病学证据与显著关联的关联强度很强（、和）。生物信息学分析表明，这些变体及其相关变体可能位于假定的功能区域。
我们的研究总结了食管癌易感性遗传结构的当前文献，并确定了几个可能与食管癌易感性相关的潜在多态性。
这些发现为未来研究确定食管癌的新遗传因素提供了方向。
