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

Chuanyang Lu; Qiuni Chen; Hong Tao; Lei Xu; Jiaxin Li; Chunling Wang; Liang Yu

doi:10.3389/fimmu.2023.1171446

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

Front Immunol. 2023 Aug 1:14:1171446. doi: 10.3389/fimmu.2023.1171446. eCollection 2023.

Authors

Chuanyang Lu^{1

2}, Qiuni Chen^{1

2}, Hong Tao^{1

2}, Lei Xu^{1

2}, Jiaxin Li^{1

2}, Chunling Wang^{1

2}, Liang Yu^{1

2}

Affiliations

¹ Department of Hematology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China.
² Key Laboratory of Hematology of Nanjing Medical University, Nanjing, China.

Abstract

Background: 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.

Methods: 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^-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.

Results: 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)_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 (OR_IVW = 1.218, 95% CI 1.030-1.441, P = 0.021) rather than ulcerative colitis (OR_IVW = 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.

Conclusions: 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.

Keywords: Mendelian randomization (MR); diffuse large B-cell lymphoma (DLBCL); genome-wide association studies (GWAS); inflammatory bowel disease (IBD); single-nucleotide polymorphisms (SNPs).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crohn Disease*
Genome-Wide Association Study
Humans
Inflammatory Bowel Diseases* / genetics
Lymphoma, Large B-Cell, Diffuse* / genetics
Mendelian Randomization Analysis

Grants and funding

This work was funded by the Young Innovative Talents Project of The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University Science [grant # QC 202218] and Commission of Health of Jiangsu Province [grant # 2019082].