PDF(Pubmed)
Abstract：
There is a close relationship between immune-mediated inflammation and cancer, and there is still controversy over whether rheumatoid arthritis (RA) increases the risk of malignancy. We first used Mendelian randomization (MR) analysis to explore the potential causal relationship between RA and pan-cancer. And verify the effect of immune-mediated inflammation on cancer through intermediate MR analysis. Then we extracted the standardized incidence rate of malignancy in RA patients relative to the general population through large-scale meta-analysis. Finally, we performed pan-cancer analysis on the RA related genes obtained from MR analysis. And perform immune related analysis on key genes to reveal the association between RA and malignancy. The MR analysis demonstrated a negative correlation between RA and pan-cancer (p = 0.008). Autoimmune traits were the main mediating variable for the causal relationship between RA and pan-cancer. Based on the results of the meta-analysis, we validated that RA reduces the risk of developing colorectal cancer (SIR = 0.69, 95% CI 0.53-0.85). Pan-cancer analysis also showed that high expression of RA related genes was negatively correlated with colon adenocarcinoma. IL6R was the gene with the highest correlation among them, and its correlation with immune cells was higher in colorectal cancer than in other malignancy. Our MR study provides evidence that RA was associated with reduced risk of colorectal cancer. This effect is caused by immune-mediated inflammation, with IL6R being a key regulatory gene.
摘要：
免疫介导的炎症与癌症之间有着密切的关系,类风湿关节炎(RA)是否会增加恶性肿瘤的风险仍存在争议。我们首先使用孟德尔随机化（MR）分析来探索RA与泛癌症之间的潜在因果关系。并通过中间MR分析验证免疫介导的炎症对癌症的影响。然后，我们通过大规模荟萃分析提取RA患者相对于普通人群的标准化恶性肿瘤发生率。最后,我们对从MR分析中获得的RA相关基因进行了全癌分析.并对关键基因进行免疫相关分析，以揭示RA与恶性肿瘤之间的关联。MR分析显示RA与泛癌症之间呈负相关（p=0.008）。自身免疫性状是RA与泛癌症之间因果关系的主要中介变量。根据荟萃分析的结果，我们验证了RA可降低结直肠癌的发病风险(SIR=0.69,95%CI0.53~0.85).泛癌分析还显示RA相关基因的高表达与结肠腺癌呈负相关。IL6R是其中相关性最高的基因,结直肠癌与免疫细胞的相关性高于其他恶性肿瘤。我们的MR研究提供了RA与降低结直肠癌风险相关的证据。这种效应是由免疫介导的炎症引起的，IL6R是一个关键的调控基因。
