Abstract
BACKGROUND: In recent years, the anti-tumor effects of vitamin D have garnered increasing attention. However, previous epidemiological studies on the relationship between vitamin D and nasopharyngeal carcinoma (NPC) have yielded inconsistent results. This study aims to further explore whether vitamin D helps reduce the risk of NPC through Mendelian randomization (MR) and meta-analysis. METHODS: Based on the core assumption of MR study, instrumental variables (IVs) for vitamin D, serving as genetic proxies, were obtained from summary data of large genome-wide association study (GWAS). Inverse-variance weighted (IVW) was utilized as the primary MR analytical method to explore the causal relationship between vitamin D and NPC. Sensitivity analyses included heterogeneity testing and horizontal pleiotropy testing. To further validate the robustness of the result, meta-analysis was employed to obtain pooled effects from databases of different sources. RESULTS: In the discovery cohort, the IVW result suggest that vitamin D is a potential protective factor against NPC (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.13-0.89, P = 0.028). The finding was further corroborated by two independent replication cohorts [OR = 0.32, 95% CI: 0.13-0.80, P = 0.018 (ukb-d-30890_irnt); OR = 0.34, 95% CI: 0.13-0.90, P = 0.029(ebi-a-GCST90025967)]. Subsequent meta-analysis indicated that vitamin D markedly reduces the risk of NPC (OR = 0.34, 95% CI: 0.19-0.58, P < 0.001). Multiple sensitivity analyses, including heterogeneity analysis and horizontal pleiotropy tests, did not reveal any significant findings (all P > 0.05). CONCLUSION: This study provides robust evidence that vitamin D significantly reduces the risk of NPC. Through MR and meta-analysis, we have demonstrated a protective role of vitamin D in NPC development. These findings suggest that maintaining adequate vitamin D levels may be a potential strategy for reducing NPC. Further research is warranted to confirm these results and explore the underlying mechanisms involved.