Department of Hematology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China.
Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.
Front Immunol. 2023 Aug 1;14:1171446. doi: 10.3389/fimmu.2023.1171446. eCollection 2023.
It has been reported that inflammatory bowel disease (IBD) is associated with an increased risk of malignancies, including lymphoma. A number of large observational studies have been devoted to exploring the causal link between IBD and malignant lymphoma. However, no consensus exists on whether there is a causal relationship between IBD and malignant lymphoma.
The summary dataset of the IBD and lymphoma genome-wide association studies (GWAS) was obtained from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) were selected as genetic instrumental variants (IVs) for fulling P < 5 × 10 and linkage disequilibrium (LD) of r = 0.001 in the IBD GWAS. The proxy SNPs with LD of r > 0.8 were identified. Palindromic SNPs and outlier SNPs were excluded. The assessments of sensitivity employed the Cochran's Q test, Mendelian randomization (MR)-Egger intercept test, and leave-one-out analysis.
The MR analysis results proved the causality of IBD on diffuse large B-cell lymphoma (DLBCL). The risk of developing DLBCL is increased by 28.6% in patients with IBD [odds ratio (OR) = 1.286, 95% confidence interval (CI) 1.066-1.552, P = 0.009]. The results of the subgroup analysis showed that Crohn's disease (OR = 1.218, 95% CI 1.030-1.441, P = 0.021) rather than ulcerative colitis (OR = 1.206, 95% CI 0.984-1.478, P = 0.072) had a causal effect on DLBCL. No horizontal and directional pleiotropy was observed in the MR studies.
The above MR study concluded that IBD itself is causally responsible for DLBCL, especially Crohn's disease. Further investigations are needed to elucidate the mechanism underlying this direct causal link.
据报道，炎症性肠病（IBD）与恶性肿瘤风险增加相关，包括淋巴瘤。许多大型观察性研究致力于探索 IBD 与恶性淋巴瘤之间的因果关系。然而，目前对于 IBD 和恶性淋巴瘤之间是否存在因果关系尚无共识。
从 OPEN GWAS 网站获得 IBD 和淋巴瘤全基因组关联研究（GWAS）的汇总数据集。单核苷酸多态性（SNP）被选为 IBD GWAS 中 P<5×10-8 和连锁不平衡（LD）r=0.001 的遗传工具变异（IV）。鉴定出具有 LD 的 r>0.8 的替代 SNP。排除回文 SNP 和异常 SNP。采用 Cochran's Q 检验、孟德尔随机化（MR）- Egger 截距检验和单倍型缺失分析进行敏感性评估。
MR 分析结果证实 IBD 与弥漫性大 B 细胞淋巴瘤（DLBCL）之间存在因果关系。IBD 患者发生 DLBCL 的风险增加了 28.6%（优势比[OR] = 1.286，95%置信区间[CI] 1.066-1.552，P = 0.009）。亚组分析结果表明，克罗恩病（OR = 1.218，95% CI 1.030-1.441，P = 0.021）而不是溃疡性结肠炎（OR = 1.206，95% CI 0.984-1.478，P = 0.072）对 DLBCL 有因果作用。MR 研究中未观察到水平和方向的异质性。
上述 MR 研究表明，IBD 本身可导致 DLBCL，尤其是克罗恩病。需要进一步研究以阐明这种直接因果关系的机制。
