Duan Jiaying, Ma Litian, Wang Tianhao, Li Tian, Li Yu
Department of Oncology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.
Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University (The Fourth Military Medical University), Xi'an, China.
Medicine (Baltimore). 2025 Jun 20;104(25):e42855. doi: 10.1097/MD.0000000000042855.
The causal link between autoimmune diseases (ADs) and diffuse large B-cell lymphoma (DLBCL) remains uncertain. This study aims to assess the causal effects of ADs on DLBCL risk using Mendelian randomization (MR). The summary dataset for ADs and lymphoma genome-wide association study (GWAS) was sourced from the open GWAS website. Single nucleotide polymorphisms were chosen as genetic instrumental variants based on linkage disequilibrium with P < 5 × 10-8 and R2 = 0.01 in different ADs GWAS. Palindrome and outlier single nucleotide polymorphisms were excluded. Cochran Q test, the MR-EGGER intercept test, MR-PRESSO, and leave-one-out analysis were used to assess sensitivity. Our results showed genetic liability to 6 ADs, including mixed connective tissue disease (odds ratios, ORWM1.578; 95% confidence intervals [CI]: 1.250-1.991, P < .001), psoriasis (ORMR-Egger = 0.775; 95% CI: 0.604-0.992, P = .049), Sjögren syndrome (ORIVW = 1.290; 95% CI: 1.072-1.551, P = .007), systemic lupus erythematosus (ORIVW = 1.153; 95% CI: 1.053-1.262, P = .002), type 1 diabetes mellitus (ORIVW = 0.899; 95% CI: 0.862-0.938, P < .001), and ulcerative colitis (ORMR-Egger = 1.648; 95% CI: 1.210-2.243, P = .003) may have a causal relationship with DLBCL. Our MR results showed that ADs, such as Sjögren syndrome and systemic lupus erythematosus, may have causal relationship with DLBCL, while type 1 diabetes mellitus could reduce the risk of DLBCL.
自身免疫性疾病（ADs）与弥漫性大B细胞淋巴瘤（DLBCL）之间的因果关系仍不明确。本研究旨在使用孟德尔随机化（MR）评估ADs对DLBCL风险的因果效应。ADs和淋巴瘤全基因组关联研究（GWAS）的汇总数据集来自开放的GWAS网站。基于不同ADs的GWAS中P < 5×10-8和R2 = 0.01的连锁不平衡，选择单核苷酸多态性作为遗传工具变量。排除回文和异常单核苷酸多态性。使用Cochran Q检验、MR-EGGER截距检验、MR-PRESSO和留一法分析来评估敏感性。我们的结果表明，6种ADs的遗传易感性，包括混合性结缔组织病（优势比，ORWM1.578；95%置信区间[CI]：1.250 - 1.991，P <.001）、银屑病（ORMR-Egger = 0.775；95% CI：0.604 - 0.992，P =.049）、干燥综合征（ORIVW = 1.290；95% CI：1.072 - 1.551，P =.007）、系统性红斑狼疮（ORIVW = 1.153；95% CI：1.053 - 1.262，P =.002）、1型糖尿病（ORIVW = 0.899；95% CI：0.862 - 0.9,38，P <.001）和溃疡性结肠炎（ORMR-Egger = 1.648；95% CI：1.210 - 2.243，P =.003）可能与DLBCL存在因果关系。我们的MR结果表明，干燥综合征和系统性红斑狼疮等ADs可能与DLBCL存在因果关系，而1型糖尿病可能降低DLBCL的风险。
