Inflammatory bowel disease increases the risk of hepatobiliary pancreatic cancer: A two-sample Mendelian randomization analysis of European and East Asian populations

Cancer Med. 2023 Jun;12(12):13599-13609. doi: 10.1002/cam4.6057. Epub 2023 May 15.

Abstract

Background: Both inflammatory bowel disease (IBD) and hepato-pancreato-biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC.

Methods: Herein, we utilized inverse-variance weighting to conduct a two-sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses.

Results: Compared to the general population, IBD patients in Europe exhibited a 1.22-fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022-1.4888 (p = 0.0475). We also found a 1.14-fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017-1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28-fold higher (95% CI = 1.0709-1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12-fold (95% CI: 1.1466-1.3334, p < 0.0001) and 1.31-fold (95% CI: 1.0983-1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19-fold higher in CD patients than in the general population (95% CI = 1.0741-1.3132, p = 0.0008).

Conclusion: Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations.

Keywords: Crohn's disease; Mendelian randomization; hepatobiliary pancreatic cancer; inflammatory bowel disease; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms
  • Bile Ducts, Intrahepatic
  • Biliary Tract Neoplasms* / epidemiology
  • Biliary Tract Neoplasms* / ethnology
  • Biliary Tract Neoplasms* / etiology
  • Biliary Tract Neoplasms* / genetics
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / ethnology
  • Carcinoma, Hepatocellular* / etiology
  • Carcinoma, Hepatocellular* / genetics
  • Crohn Disease / epidemiology
  • East Asian People / genetics
  • East Asian People / statistics & numerical data
  • European People / genetics
  • European People / statistics & numerical data
  • Humans
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / epidemiology
  • Inflammatory Bowel Diseases* / ethnology
  • Inflammatory Bowel Diseases* / genetics
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / ethnology
  • Liver Neoplasms* / etiology
  • Liver Neoplasms* / genetics
  • Mendelian Randomization Analysis
  • Pancreatic Neoplasms* / epidemiology
  • Pancreatic Neoplasms* / ethnology
  • Pancreatic Neoplasms* / etiology
  • Pancreatic Neoplasms* / genetics