Yang Lei, Yang Zelin, Zuo Chunjian, Lv Xiaolong, Liu Tianyu, Jia Chenhao, Chen Huanwen
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Thoracic Surgery, Army Medical Center of People's Liberation Army of China (PLA), Chongqing, China.
Front Oncol. 2022 Oct 6;12:1001864. doi: 10.3389/fonc.2022.1001864. eCollection 2022.
Genetic studies have previously reported that single-nucleotide polymorphisms (SNPs) in genes (such as , , , or clusters) are linked to the risk of neoplastic and non-neoplastic diseases. However, these conclusions were controversial and no systematic research synopsis has been available. We aimed to synthesize current knowledge of variants in the genes on the risk of diseases.
We systematically searched for publications using PubMed, Medline, and Web of Science on or before 25 August 2021. A total of 1,818 publications were identified, of which 29 were deemed eligible for inclusion that could be used to perform meta-analysis based on at least three data sources to assess whether the morbidity associated with neoplastic and non-neoplastic diseases can be attributed to SNPs in genes. To further evaluate the authenticity of cumulative evidence proving significant associations, the present study covered the Venice criteria and false-positive report probability tests. Through the Encyclopedia of DNA Elements (ENCODE) project, we created functional annotations for strong associations.
Meta-analyses were done for nine genetic variants with two diseases {chronic obstructive pulmonary disease (COPD) and lung cancer (LC)}that had at least three data sources. Interestingly, eight polymorphisms were significantly related to changes in the susceptibility COPD and LC ( < 0.05). Of these, strong evidence was assigned to six variants (28 significant associations): rs1051730, rs6495309, and rs16969968 with COPD risk, and rs1051730, rs578776, rs6495309, rs938682, rs16969968, and rs588765 with LC risk; moderate evidence was assigned to five SNPs (12 total associations) with LC or COPD risk. Data from ENCODE and other public databases showed that SNPs with strong evidence may be located in presumptive functional regions.
Our study summarized comprehensive evidence showing that common mutations in genes are strongly related to LC and COPD risk. The study also elucidated the vital function of genes in genetic predispositions to human diseases.
此前的基因研究报告称，某些基因（如 、 、 或 基因簇）中的单核苷酸多态性（SNP）与肿瘤性和非肿瘤性疾病的风险相关。然而，这些结论存在争议，且尚无系统的研究综述。我们旨在综合目前关于 基因变异与疾病风险的知识。
我们使用PubMed、Medline和Web of Science系统检索了截至2021年8月25日或之前的出版物。共识别出1818篇出版物，其中29篇被认为符合纳入标准，可用于进行荟萃分析，这些研究基于至少三个数据源来评估肿瘤性和非肿瘤性疾病的发病率是否可归因于 基因中的SNP。为了进一步评估证明显著关联的累积证据的真实性，本研究涵盖了威尼斯标准和假阳性报告概率检验。通过DNA元件百科全书（ENCODE）项目，我们对强关联创建了功能注释。
对九种基因变异与两种疾病{慢性阻塞性肺疾病（COPD）和肺癌（LC）}进行了荟萃分析，这些疾病有至少三个数据源。有趣的是，八个多态性与COPD和LC易感性的变化显著相关（ < 0.05）。其中，六个变异（28个显著关联）有强有力的证据：rs1051730、rs6495309和rs16969968与COPD风险相关，rs1051730、rs578776、rs6495309、rs938682、rs16969968和rs588765与LC风险相关；五个SNP（共12个关联）有中等证据与LC或COPD风险相关。来自ENCODE和其他公共数据库的数据表明，有强有力证据的SNP可能位于推定的功能区域。
我们的研究总结了全面的证据，表明 基因中的常见突变与LC和COPD风险密切相关。该研究还阐明了 基因在人类疾病遗传易感性中的重要作用。
