Periodontitis and Hepatocellular Carcinoma: A Two-Sample Mendelian Randomisation Study

Abstract

Introduction and AimsObservational studies have reported conflicting associations between periodontitis (PD) and hepatocellular carcinoma (HCC). To overcome these limitations, we performed a two-sample Mendelian randomization (MR) analysis to investigate the potential association between PD and HCC. MethodsWe used summary data from genome-wide association studies (GWASs) of European ancestry, integrating data from chronic/acute periodontitis (CP/AP) samples (n1 = 34,615; n2 = 277,036; n3 = 410,811) and HCC samples (n1 = 456,348; n2 = 475,638). The inverse variance-weighted (IVW) approach represents our primary analysis method, supplemented by MR-Egger regression, weighted median, weighted-mode, and simple-mode methods. Pleiotropy and heterogeneity tests were also performed. ResultsIVW analysis suggested that PD had no effect on HCC (Group 1: odds ratio [OR] = 0.912, 95% confidence interval [CI] = 0.690-1.204, P = .514; Group 2: OR = 1.038, 95% CI = 0.895-1.203, P = .623; Group 3: OR = 0.966, 95% CI = 0.851-1.096, P = .591; Group 4: OR = 1.103, 95% CI = 0.576-2.113, P = .768; Group 5: OR = 1.257, 95% CI = 0.511-1.037, P = .540; Group 6: OR = 0.728, 95% CI = 0.511-1.037, P = .079). Four complementary analyses further support this conclusion. Both the IVW and MR-Egger results indicate that the instrumental variables in each group did not exhibit significant pleiotropy. MR-Egger regression analysis showed no evidence of pleiotropic effects. ConclusionOur MR analysis suggests that PD does not significantly impact the risk of developing HCC. These results provide a new perspective on the relationship between these 2 conditions. Clinical RelevanceThis MR study suggests no significant genetic causal relationship between PD and HCC, providing a new perspective. It indicates that clinicians may not need to over-intervene in periodontal disease to prevent liver cancer, thereby avoiding unnecessary psychological burden on patients.