Association Between Oral Cavity Cancer and Lymphoma: A Bidirectional Mendelian Randomization Analysis

Abstract

Purpose Emerging evidence suggests a potential association between oral cavity cancer (OCC) and lymphoma. This study aimed to investigate whether this association reflects a causal relationship. Materials and Methods A two-sample bidirectional Mendelian randomization (MR) approach was utilized to screen genetic instrumental variables (IVs) obtained from genome-wide association studies (GWAS) of OCC and lymphoma, applied various MR methods (inverse variance weighted [IVW] as the main method) to assess the causal relationship between the two malignancies, and performed sensitivity, heterogeneity, and pleiotropic tests to evaluate reliability. Results No bidirectional causal association between OCC and Hodgkin lymphoma (HL) or overall non-Hodgkin lymphoma (NHL) was found. Subgroup analysis also showed that no noteworthy bidirectional causal relationship between OCC and NHL subtypes. However, we identified a statistically significant inverse correlation between mature T/NK-cell lymphoma and OCC (IVW: odds ratio [OR] 0.985, 95% confidence interval [CI]: 0.820-0.978, p=0.013). Patients initially diagnosed with mature T/NK-cell lymphoma would have a decreased risk of OCC. Conclusion This MR study ruled out the causal relationship between OCC and lymphoma. Future multiethnic studies with substantial sample sizes are need to replicate our findings.