Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Department of General Surgery, Jing'an Branch, Huashan Hospital, Fudan University, Shanghai 200060, China.
Genes (Basel). 2023 Sep 23;14(10):1844. doi: 10.3390/genes14101844.
Whether the positive associations of gastric cancer (GC) with autoimmune diseases are causal has always been controversial. This study aims to estimate the causal relationship between GC and 12 autoimmune diseases by means of Mendelian randomization (MR) analysis.
After rigorous evaluation, potential candidate single nucleotide polymorphisms (SNPs) for GC and 12 autoimmune diseases were extracted from genome-wide association study (GWAS) datasets. We performed the MR analyses using the inverse variance weighted (IVW) method as the primary approach to the analysis. Three sensitivity analysis methods were added to assess the robustness of the results. In addition, heterogeneity was measured using Cochran's Q-value, and horizontal pleiotropy was assessed using MR-Egger regression and leave-one-out analysis.
The IVW result, which is the main method of analysis, shows no evidence of a causal association between GC and any autoimmune disease. The results of IVW analysis show the relationship between rheumatoid arthritis ( = 0.1389), systemic lupus erythematosus ( = 0.1122), Crohn's disease ( = 0.1509), multiple sclerosis ( = 0.3944), primary sclerosing cholangitis ( = 0.9022), primary biliary cirrhosis ( = 0.7776), type 1 diabetes ( = 0.9595), ulcerative colitis ( = 0.5470), eczema ( = 0.3378), asthma ( = 0.7436), celiac disease ( = 0.4032), and psoriasis ( = 0.7622) and GC susceptibility. The same result was obtained with the weighted median and the MR-egger ( > 0.05).
Our study did not find a genetic causal relationship between susceptibility to these autoimmune diseases and GC, which suggests that unmeasured confounders (e.g., inflammatory processes) or shared genetic architecture may be responsible for the reported epidemiologic associations. Further studies of ancestral diversity are warranted to validate such causal associations.
胃癌（GC）与自身免疫性疾病之间的正相关性是否具有因果关系一直存在争议。本研究旨在通过孟德尔随机化（MR）分析来估计 GC 与 12 种自身免疫性疾病之间的因果关系。
经过严格评估，从全基因组关联研究（GWAS）数据集中提取了潜在的候选 GC 和 12 种自身免疫性疾病的单核苷酸多态性（SNP）。我们使用逆方差加权（IVW）方法作为主要分析方法进行了 MR 分析。添加了三种敏感性分析方法来评估结果的稳健性。此外，使用 Cochran's Q 值测量异质性，并使用 MR-Egger 回归和逐一剔除分析评估水平偏倚。
主要分析方法 IVW 结果表明，GC 与任何自身免疫性疾病之间没有因果关系的证据。IVW 分析结果表明，类风湿关节炎（ = 0.1389）、系统性红斑狼疮（ = 0.1122）、克罗恩病（ = 0.1509）、多发性硬化症（ = 0.3944）、原发性硬化性胆管炎（ = 0.9022）、原发性胆汁性肝硬化（ = 0.7776）、1 型糖尿病（ = 0.9595）、溃疡性结肠炎（ = 0.5470）、湿疹（ = 0.3378）、哮喘（ = 0.7436）、乳糜泻（ = 0.4032）和银屑病（ = 0.7622）与 GC 易感性之间存在关联。加权中位数和 MR-egger （> 0.05）也得到了相同的结果。
我们的研究没有发现这些自身免疫性疾病易感性与 GC 之间存在遗传因果关系，这表明未测量的混杂因素（例如炎症过程）或共同的遗传结构可能是导致报告的流行病学关联的原因。需要进一步研究祖先多样性来验证这种因果关系。
