Inflammatory Bowel Disease and Skin Cancer: A Two-Sample Mendelian Randomization Analysis.

ABSTRACT

Background: At present, numerous clinical studies suggest a correlation between inflammatory bowel disease (IBD) and skin cancer. However, some articles present differing views that IBD does not increase the risk of skin cancer. The presence of potential reverse causality and residual confounding is inherent in conventional observational studies. Thus, this study used a two-sample Mendelian randomization (MR) study design to estimate the causal effect of IBD on the risk of skin cancer, including cutaneous malignant melanoma (CMM, also named melanoma skin cancer) and nonmelanoma skin cancer (NMSC). Design: In this study, a two-sample MR analysis was used to estimate the causal effect of IBD on skin cancer outcomes. The inverse-variance weighted (IVW) method was used as the main MR analysis, with multiple sensitivity analyses conducted to assess the robustness of findings. Results: In examining the association between IBD and NMSC, all p-values of the IVW methods were found to be <0.05, providing evidence for a causal effect of IBD on an increased risk of NMSC. However, IVW for IBD on CMM yielded p-values >0.05, indicating no causal relationship between IBD and CMM. These findings were consistent across other MR methods, with no evidence of pleiotropy or heterogeneity. Sensitivity analyses confirmed the robustness of our results. Conclusion: Using MR analysis, we found evidence for a causal effect of genetic liability for IBD on an increased risk of NMSC. However, our study did not find sufficient evidence to support a significant impact of IBD on CMM outcomes.