Two-sample Mendelian randomization study reveals no causal relationship between inflammatory bowel disease and urological cancers

Abstract

Background: The relationship between inflammatory bowel disease (IBD) and urological cancers has been identified in epidemiological and observational studies, while the causality remains uncertain. We examined whether IBD is causally associated with urological cancers in a Mendelian randomization (MR) study. Methods: The causal relationship between IBD, its main subtypes, and urological cancers was investigated using genome-wide association study data. To obtain more reliable conclusions, all outcomes were divided into training and validation sets. Eligible single-nucleotide polymorphisms were selected as instrumental variables based on MR analysis assumptions. The inverse variance-weighted (IVW) method was employed as the main method along with four other complementary methods. Results: In this two-sample MR study, no genetic evidence for the causal effect of IBD on urological cancers was found in either the training or validation sets using the IVW method. Similarly, we did not observe any significant association between Crohn's disease or ulcerative colitis and urological cancers. The results of the other methods are in accordance with those obtained using the IVW method. Conclusion: In this study, we confirmed that IBD is not a causal genetic risk factor for urological cancer in a European population.

Keywords: Mendelian randomization; causality; inflammatory bowel disease; single-nucleotide polymorphisms; urological cancers.

FIGURE 1

Flowchart of the Mendelian randomization analysis of Crohn’s disease and ulcerative colitis and the risk of development of kidney cancer, bladder cancer, and prostate cancer. IIBDGC, International Inflammatory Bowel Disease Genetics Consortium; IBD, inflammatory bowel disease; PRACTICAL, Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome; LD, linkage disequilibrium; and SNPs, single-nucleotide polymorphisms.

FIGURE 2

Forest plot: causal associations of inflammatory bowel disease and its main subtypes with urological cancers using the IVW method. (A) Effect of inflammatory bowel disease on urological cancers. (B) Effect of Crohn’s disease on urological cancers. (C) Effect of ulcerative colitis on urological cancers. PRACTICAL, Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome; IVW, inverse variance-weighted; OR, odds ratio; and CI, confidence interval.