Association between inflammatory bowel disease and cancer risk - evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations

Sep 21, 2026

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), has been linked to multiple cancer risks in observational studies, yet findings remain inconsistent due to likely confounding and reverse causality. Causal relationships between IBD and cancer risk are largely unresolved. This study triangulates genetic evidence across East Asian and European populations to assess causality between IBD phenotypes and cancers, using genetic correlation, Mendelian randomization, and colocalization.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Background

Cancer burden and early risk identification

IBD characteristics and disease burden

Rationale for genetic approaches

Liu et al. BMC Medicine (2024) 22:137 [https://doi.org/10.1186/s12916-024-03352-9](https://doi.org/10.1186/s12916-024-03352-9) BMC Medicine RESEARCH ARTICLE Open Access Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations Di Liu1†, Meiling Cao2†, Haotian Wang2, Weijie Cao3, Chenguang Zheng4, Yun Li4 and Youxin Wang3,4,5* 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. Keywords Inflammatory bowel disease, Cancers, Mendelian randomization, Genetic correlation, Colocalization analysis †Di Liu and Meiling Cao contributed equally to this work. *Correspondence: Youxin Wang [wangyouxin@ncst.edu.cn](wangyouxin@ncst.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://creativecom](http://creativecom)[mons.org/publicdomain/zero/1.0/](mons.org/publicdomain/zero/1.0/)

FAQs

Why are observational links between IBD and cancer considered uncertain?

Observational studies may suffer from confounding and reverse causality, and prior findings across cancers have been inconsistent, leaving causality unclear.

What methods were used to evaluate causal relationships?

The study used genome-wide linkage disequilibrium score regression (LDSC), two-sample Mendelian randomization (MR), and colocalization analyses based on summary GWAS data, with additional sensitivity analyses for MR stability.

What were the main genetic findings regarding IBD and cancer?

No significant genetic correlations were found between IBD/CD/UC and cancers in East Asian or European populations. MR identified associations in Europeans for CD–ovarian cancer and UC–nonmelanoma skin cancer, but multivariable MR and colocalization did not support robust causal evidence.

Sep 21, 2026

Uploaded by Lucas Martin