Document Type
Journal Article
Publication Title
BMC Medicine
Volume
22
Issue
1
Publisher
Springer / BMC
School
Graduate Research School / School of Medical and Health Sciences
RAS ID
65709
Funders
China Postdoctoral Science Foundation / National Key R&D Program of China
Abstract
Background: Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear. Methods: We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results. Results: There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844–0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000–1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis. Conclusions: We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.
DOI
10.1186/s12916-024-03352-9
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Liu, D., Cao, M., Wang, H., Cao, W., Zheng, C., Li, Y., & Wang, Y. (2024). Association between inflammatory bowel disease and cancer risk: Evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations. BMC Medicine, 22, article 137. https://doi.org/10.1186/s12916-024-03352-9