先前的研究表明，被诊断患有类风湿性关节炎 (RA) 的个体肿瘤患病率较高。本研究的主要目的是深入研究 RA 与两种不同类型的肿瘤之间的因果关系：骨和关节软骨良性肿瘤 (BNBAC) 和骨和关节软骨恶性肿瘤 (MNBAC)。我们采用了来自基因组的汇总数据全关联分析 (GWAS) 使用两样本双向孟德尔随机化 (MR) 研究设计来调查 RA 与两种肿瘤（BNBAC 和 MNBAC）之间的因果关系。 IEU OpenGWAS 数据库提供了 RA 的 GWAS 摘要数据，而芬兰财团提供了 BNBAC 和 MNBAC 的 GWAS 摘要数据。我们的分析涉及使用八种不同的 MR 方法，即随机效应逆方差加权 (IVW)、MR Egger、加权中位数、简单模式、加权模式、最大似然、惩罚加权中位数和固定效应 IVW。随后，我们进行了评估，以评估 MR 分析中的异质性、水平多效性、异常值、单核苷酸多态性 (SNP) 的影响以及对正态分布假设的遵守情况。MR 分析的结果表明，不存在RA 和 BNBAC 之间存在显着的遗传关联（P = 0.427，比值比 [OR] 95% 置信区间 [CI] = 0.971 [0.904-1.044]）。然而，在 RA 和 MNBAC 之间观察到正向遗传关联（P = 0.001，OR 95% CI = 1.413 [1.144-1.745]）。进行反向 MR 分析，我们发现没有证据支持 BNBAC（P = 0.088，OR 95% CI = 1.041 [0.994-1.091]）或 MNBAC（P = 0.168，OR 95% CI = 1.013 [0.995-] 之间存在遗传因果关系。 1.031]）和RA。我们的 MR 分析证明不存在异质性、水平多效性和异常值，并证实该效应不是由单个 SNP 驱动的。此外，数据呈正态分布。本研究的结果表明，RA 是 MNBAC 的一个重要危险因素。在临床应用中，建议对RA患者进行MNBAC筛查，并对其潜在表现保持警惕。重要的是，这项研究的结果为理解与 RA 相关的肿瘤发生提供了一个新的视角。© 2023。作者。

Prior research has revealed a heightened prevalence of neoplasms in individuals diagnosed with rheumatoid arthritis (RA). The primary objective of this study is to delve into the causal association between RA and two distinct types of neoplasms: benign neoplasm of bone and articular cartilage (BNBAC) and malignant neoplasm of bone and articular cartilage (MNBAC).We employed summary data from genome-wide association analyses (GWAS) to investigate the causal relationship between RA and two neoplasms, BNBAC and MNBAC, using a two-sample bidirectional Mendelian randomization (MR) study design. The IEU OpenGWAS database provided the GWAS summary data for RA, while the Finnish consortium supplied the GWAS summary data for BNBAC and MNBAC. Our analysis involved the utilization of eight distinct MR methods, namely random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed effects IVW. Subsequently, we conducted assessments to evaluate heterogeneity, horizontal pleiotropy, outliers, the impact of a single-nucleotide polymorphism (SNP), and adherence to the assumption of normal distribution in the MR analysis.The results from the MR analysis revealed that there was no significant genetic association between RA and BNBAC (P = 0.427, odds ratio [OR] 95% confidence interval [CI] = 0.971 [0.904-1.044]). However, a positive genetic association was observed between RA and MNBAC (P = 0.001, OR 95% CI = 1.413 [1.144-1.745]). Conducting a reverse MR analysis, we found no evidence to support a genetic causality between BNBAC (P = 0.088, OR 95% CI = 1.041 [0.994-1.091]) or MNBAC (P = 0.168, OR 95% CI = 1.013 [0.995-1.031]) and RA. Our MR analysis demonstrated the absence of heterogeneity, horizontal pleiotropy, and outliers and confirmed that the effect was not driven by a single SNP. Additionally, the data exhibited a normal distribution.The findings of this study demonstrate that RA constitutes a significant risk factor for MNBAC. In the context of clinical application, it is advisable to conduct MNBAC screening in RA patients and remain vigilant regarding its potential manifestation. Importantly, the outcomes of this investigation introduce a fresh vantage point into the understanding of the tumorigenesis associated with RA.© 2023. The Author(s).