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

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.

Causal effects of gut microbiota in the development of lung cancer and its histological subtypes: A Mendelian randomization study

“…This approach allows for the effective avoidance of confounding agents, which can be elusive to control for in observational studies. 15 Since alleles that affect genetic variants are distributed randomly to offspring at gestation, regardless of environmental and other uncharted confounders, MR analyses are analogous to natural randomized controlled trials. 16 Such analyses permit the assessment of causality between exposures and outcomes at the genetic level while ruling out the likelihood of reverse causality.…”

Meta‐analysis: Risk of pancreatic cancer in patients with inflammatory bowel disease

“…Lastly, genetic factors that predispose individuals to IBD might also be linked to an increased risk of pancreatic cancer 36,37 . Our study revealed that IBD is associated with a raised risk of pancreatic cancer based on MR studies 28,29 . Exacerbating inflammation in the pancreas caused by shared genetic factors may contribute to the development of pancreatic cancer.…”

“…For this systematic review and meta‐analysis, we screened 5201 citations from the initial database search. After excluding 5188 publications because of duplication or unsuitability, we identified 13 eligible articles, including 11 cohort studies regarding the first study aim 5,8–11,22–27 and two studies concerning the second study aim 28,29 . The search strategy and process for study selection are illustrated in Figure 1.…”

“…Two eligible large‐scale MR studies were found assessing the relationship between IBD and the risk of pancreatic cancer (Table 2). According to the study by Huang et al., 28 the results of the IVW estimates demonstrated that genetic liability to IBD was associated with an increased risk of pancreatic cancer development (odds ratio [OR] = 1.18 [95% CI: 1.04–1.34]). The MR study by Min et al 29 .…”

Classification of Long-term Disease Patterns in Inflammatory Bowel Disease and Analysis of their Associations with Adverse Health Events: a UK Biobank Cohort Study

“…It also manifests extraintestinally, primarily affecting areas such as the eyes, skin, joints, and biliary system [4]. The systemic chronic in ammation induced by IBD increases the risk of developing other long-term conditions (LTCs), including cardiovascular diseases [5], diabetes [6], cancers [7,8], liver diseases [9], respiratory disorders [10], and musculoskeletal diseases [11]. The systemic chronic in ammation caused by IBD disrupts the balance of neurotransmitter secretion involved in emotional regulation and cognitive function, potentially leading to the occurrence of depression and anxiety [12,13].…”