Yi Ting, Lin Shaoxiong
Department of Otorhinolaryngology Head and Neck Surgery, Southern University of Science and Technology Hospital, Shenzhen, China.
Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Discov Oncol. 2024 Nov 9;15(1):637. doi: 10.1007/s12672-024-01511-1.
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.
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.
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).
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.
近年来，维生素D的抗肿瘤作用日益受到关注。然而，以往关于维生素D与鼻咽癌（NPC）关系的流行病学研究结果并不一致。本研究旨在通过孟德尔随机化（MR）和荟萃分析进一步探讨维生素D是否有助于降低NPC的发病风险。
基于MR研究的核心假设，从大型全基因组关联研究（GWAS）的汇总数据中获取作为基因代理的维生素D工具变量（IVs）。采用逆方差加权（IVW）作为主要的MR分析方法，探讨维生素D与NPC之间的因果关系。敏感性分析包括异质性检验和水平多效性检验。为进一步验证结果的稳健性，采用荟萃分析从不同来源的数据库中获得合并效应。
在发现队列中，IVW结果表明维生素D是NPC的潜在保护因素（优势比（OR）=0.35，95%置信区间（CI）：0.13 - 0.89，P = 0.028）。这一发现得到了两个独立重复队列的进一步证实[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）]。随后的荟萃分析表明，维生素D显著降低了NPC的发病风险（OR = 0.34，95% CI：0.19 - 0.58，P < 0.001）。包括异质性分析和水平多效性检验在内的多项敏感性分析均未发现显著结果（所有P > 0.05）。
本研究提供了有力证据，表明维生素D可显著降低NPC的发病风险。通过MR和荟萃分析，我们证明了维生素D在NPC发生发展中的保护作用。这些发现表明，维持充足的维生素D水平可能是降低NPC的一种潜在策略。有必要进行进一步研究以证实这些结果并探索其中的潜在机制。
