Causal associations of Graves’ Disease with hepatobiliary carcinoma in East Asian population: a Mendelian randomization study

Abstract

Background Graves' disease, a thyroid autoimmune disease, has been shown to be associated with a variety of cancers, whereas the association of the disease with hepatobiliary carcinoma (HC) remains unexplored. In this research, we systematically analyze causal links of Graves’ Disease (GD) with HC by means of a Mendelian randomization (MR). Methods In this study, we utilize five methods such as MR-Egger, Inverse variance weighting (IVW), Weighted median, Simple mode and Weighted mode to explore the connection between the exposure factor and the outcome variable. Then we observe the sensitivity, heterogeneity and multiple effects between causes and effects by applying Cochran's Q-test, leave-one-out analysis and MR Egger intercept test. We carried out forward MR analysis which employed GD as the risk factor, and HCC (hepatocellular carcinoma) and BTC (biliary tract cancer) as the outcome variables. Then the reverse MR analysis we carried out was the opposite. Results The IVW approach in the forward MR analysis pointed that there has a possible relationship between GD and BTC (IVW: OR = 0.83, 95% CI: 0.729–0.945, p = 0.005), while the study also pointed that GD may be causally related to HCC (IVW: OR = 0.882, 95% CI: 0.799–0.974, p = 0.013). Subsequent MR Egger regression analyses conducted noted no significant multicollinearity between instrumental variables (IV) (BTC: Egger intercept = 0.041, p = 0.221; HCC: Egger intercept = -0.028, p = 0.793): Egger intercept = -0.028, p = 0.793). Our sensitivity analysis which use leave-one-out analysis pointed that culling any of the 29 single nucleotide polymorphisms (SNPs) in the GD did not obviously reverse the outcomes, indicating that there was no significant heterogeneity in this analysis. Conclusion GD may be a protective factor for HC, and these discovers inspirit us to carry out clinical studies between GD and HC.