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

Abstract

BackgroundThe 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.MethodsThe 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.ResultsIn 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.ConclusionThis 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.

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.…”

“…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 . also showed that patients with a genetic predisposition to IBD, especially CD, are at an increased risk of developing 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.…”

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

“…During analyses of causal effects between CD and extraintestinal cancers, we discovered that the incidence of pancreatic cancer in patients with CD is 1.10 times higher in the European population and 1.19 times higher in the East Asian population compared to individuals without CD. Similarly, Yu's MR study showed a causal effect between CD and pancreatic cancer risk (OR: 1.111; 95% CI: 1.015-1.213) in Europeans (47). Two studies, one involving Scandinavians and the other Koreans, also consistently reported that CD increases the risk of pancreatic cancer (48, 49).…”