Causal association between Vitamin D levels and head-and-neck cancer: A Mendelian randomization study

Observational studies have revealed inconsistent findings regarding the association between Vitamin D levels and head-and-neck cancer (HNC). Therefore, this study aimed to examine the possible causality of Vitamin D for HNC risk using two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Single-nucleotide polymorphisms closely associated with Vitamin D levels were selected from the genome-wide association research database as instrumental variables. The analytical approaches utilized included inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analysis was performed to verify the robustness of MR findings. In addition, the causation of Vitamin D on HNC risk was assessed by controlling for the influences of smoking and alcohol intake through MVMR analysis. IVW (odds ratio = 0.9958, 95% confidence interval = 0.9934 – 0.9983, p = 0.0007) indicated that Vitamin D levels were negatively related to HNC risk. The weighted median yielded the same result. The results of the MVMR analysis further supported the role of Vitamin D in mitigating HNC risk. The sensitivity analysis revealed the absence of heterogeneity or pleiotropy of the instrumental variables, proving our results reliable without significant bias. This study offers genetic evidence in favor of the causality of Vitamin D for HNC risk. Increasing Vitamin D intake may help lower HNC risk.