Exploring genetic associations of Crohn’s disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations - Original Research

Sep 21, 2026

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Genetically predicted Crohn’s disease (CD) and ulcerative colitis (UC) are evaluated for causal relationships with nine extraintestinal cancer types in European and East Asian populations. Background evidence shows associations between CD/UC and extraintestinal cancer risk, but causality remains uncertain. Two-sample Mendelian randomization uses CD/UC genetic variants as instrumental variables, with inverse variance weighted as the primary method and sensitivity analyses to test robustness. Results identify population-specific causal patterns and support enhanced screening and prevention of site-specific extraintestinal cancers.

LanguageEnglish

CategoryResearch & Report

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Pages11

Reading Time28 min

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Background

Methods

Results

Conclusions

Introduction

TYPE Original Research PUBLISHED 08 February 2024 DOI 10.3389/fimmu.2024.1339207 OPEN ACCESS EDITED BY Shahanshah Khan, University of Texas Southwestern Medical Center, United States REVIEWED BY Vincent Salvatore Gallicchio, Clemson University, United States Marcos Edgar Herkenhoff, University of São Paulo, Brazil *CORRESPONDENCE Zhengkui Sun [sunzhengkui@sohu.com](sunzhengkui@sohu.com) †These authors have contributed equally to this work RECEIVED 15 November 2023 ACCEPTED 19 January 2024 PUBLISHED 08 February 2024 CITATION Yu C, Xu J, Xu S, Tang L, Han Q, Zeng X, Huang Y, Yu T and Sun Z (2024) Exploring genetic associations of Crohn’s disease and ulcerative colitis with extraintestinal cancersin European and East Asian populations. Front. Immunol. 15:1339207 . doi: 10.3389/fimmu.2024.1339207 COPYRIGHT © 2024 Yu, Xu, Xu, Tang, Han, Zeng, Huang, Yu and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Exploring genetic associations of Crohn’s disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations Chengdong Yu 1†, Jiawei Xu 1†, Siyi Xu 1†, Lei Tang 1, Qinyuan Han 1, Xiaoqiang Zeng 1, Yanxiao Huang 1, Tenghua Yu 2 and Zhengkui Sun 2* 1Jiangxi Medical College, Nanchang University, Nanchang, China, 2 Department of breast surgery, Jiangxi Cancer Hospital, Nanchang, China Background: Previous studies have reported associations of Crohn’s disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods: Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our ﬁndings. Results: In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1 . 1042; 95% CI: 1 .0087-1. 2088; P=0 . 0318) . Meanwhile, both CD (outliers excluded: OR: 1 . 0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1 . 1091; 95% CI: 1 .0286-1. 1960; P=0 . 0071) . In the East Asian population, CD had signiﬁcant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0 . 9452; 95% CI: 0 .9096-0. 9822; P=0 . 0040) . For UC, it exhibited signiﬁcant causal associations with gastric cancer (OR: 1 . 1240; 95% CI: 1 .0624- 1. 1891; P=4 .7359×10–5), bile duct cancer (OR: 1 .3107; 95% CI: 1 .0983-1. 5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1 . 4007×10–5) and cervical cancer (OR: 1 . 3941; 95% CI: 1 .1708-1. 6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1 . 1313; 95% CI: 1 .0280-1. 2449; P=0 . 0116) . Conclusions: Our study provided evidence that genetically predicted CD may bea risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) factor for cervical and breast cancers in Euro

FAQs

What question does the study address about Crohn’s disease and ulcerative colitis?

The study examines whether genetically driven CD and UC have causal relationships with risks of extraintestinal cancers, noting that prior associations exist but causality is unclear.

How were genetic variants used in this analysis?

The analysis uses genetic variations robustly associated with CD and UC from genome-wide association studies as instrumental variables in a two-sample Mendelian randomization framework.

Which extraintestinal cancers showed evidence of causal associations?

In Europeans, CD showed potential causal association with pancreatic cancer and a slight increase in breast cancer risk, while UC showed a potential causal effect on cervical cancer. In East Asians, CD showed causal effects on pancreatic cancer and breast cancer, and UC showed causal associations with gastric, bile duct, hepatocellular, cervical, and a potential effect on lung cancer.

Sep 21, 2026

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