Abstract
OBJECTIVES: The purpose of this study is to assess the potential causal relationship between immune cell phenotype and oral cancer using Mendelian randomisation analysis. METHODS: A two-sample Mendelian randomisation (MR) analysis using summary statistics from genome-wide association studies in European populations was conducted to explore causal relationships between immune cell phenotypes and the risk of oral cancer. Inverse-variance weighting, MR-EGGER, simple mode, weighted median, and weighted mode were applied for MR analysis. Sensitivity analyses, including the Steiger test, Cochran's Q test, Egger intercept, and leave-one-out analysis, were performed to assess the robustness of the results. Additionally, colocalisation analysis was carried out to further validate causal associations. RESULTS: A total of 21 immune cell phenotypes were identified as risk factors for oral cancer, while 6 immune cell phenotypes demonstrated protective effects. Sensitivity analyses indicated a lack of robustness in four causal relationships. Genetic variants at rs9469077 on chr6 might be shared between CD28(-)CD127(-)CD25(++)CD8br AC of regulatory T cells and oral cancer. CONCLUSION: This MR study provides evidence for a strong association between immune cells and oral cancer, highlighting specific immune cell phenotypes as significant risk factors for the development of oral cancer. These findings offer a foundation for future precision immunotherapy strategies for oral cancer. Further studies are required to confirm the relationship between immune cells and oral cancer risk and to elucidate the underlying mechanisms. CLINICAL RELEVANCE: This study confirms the potential relationship between specific immune cell phenotypes and oral cancer, providing theoretical support for future immunotherapy against oral cancer.