The causal effect of inflammatory bowel disease on diffuse large B-cell lymphoma: two-sample Mendelian randomization study

Abstract

BackgroundIt 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.MethodsThe 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 × 10-8 and linkage disequilibrium (LD) of r2 = 0.001 in the IBD GWAS. The proxy SNPs with LD of r2 > 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.ResultsThe 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)IVW = 1.286, 95% confidence interval (CI) 1.066–1.552, P = 0.009]. The results of the subgroup analysis showed that Crohn’s disease (ORIVW = 1.218, 95% CI 1.030–1.441, P = 0.021) rather than ulcerative colitis (ORIVW = 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.ConclusionsThe 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.