Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study

Yu Min; Zheran Liu; Ruidan Li; Jing Jin; Zhigong Wei; Yiyan Pei; Xiaolin Hu; Xingchen Peng

doi:10.3389/fonc.2023.1155123

Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study

Front Oncol. 2023 Aug 23:13:1155123. doi: 10.3389/fonc.2023.1155123. eCollection 2023.

Authors

Yu Min¹, Zheran Liu¹, Ruidan Li¹, Jing Jin¹, Zhigong Wei¹, Yiyan Pei¹, Xiaolin Hu², Xingchen Peng¹

Affiliations

¹ Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China.
² West China School of Nursing, West China Hospital, Sichuan University, Cheng Du, Sichuan, China.

Abstract

Background: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear.

Methods: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results.

Results: In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses.

Conclusion: This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.

Keywords: Crohn’s disease; GWAS; inflammatory bowel disease; mendelian randomization; pancreatic cancer; risk factor; ulcerative colitis.

Grants and funding

The work was supported by the National Key Research and Development Program of China (2021YFE0206600), and the National Natural Science Foundation of China (82172842 and 81672386). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.