Page 203 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Vitamin D and HNC: Causal association

Figure 6. Results of the multivariable Mendelian randomization analysis

regression models adjusted for potential confounders such immune function. When supplemented with Vitamin D,
as age, body mass index, smoking volume, and alcohol patients’ natural killer cells expressed significantly enhanced
consumption. The results indicated the lack of significant cytotoxic activity. In addition, the infiltration of activated
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associations between serum 25(OH)D levels and the CD4+CD69+ T cells and regulatory Foxp3+CD4+ T cells
risk of either overall HNC or specific subtypes (e.g., oral in HNSCC tissue was related to a better prognosis. In
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cavity, pharynx, and larynx cancers). However, a meta- patients with HNC and high Vitamin D levels, higher CD+4
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analysis of 16 studies revealed that higher Vitamin D cell counts in the tumor and peritumoral mesenchyme
intake was associated with a reduced incidence of HNC. were strongly associated with longer overall survival. This
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5
This meta-analysis showed that individuals with higher finding indicates that Vitamin D significantly regulates
serum 25(OH)D levels had a 32% lower incidence of HNC the immune response to tumors. Vitamin D upregulates
than those with lower serum 25(OH)D levels. In addition, antioxidant pathways and limits oxidative DNA damage,
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patients with higher 25(OH)D levels had significantly thereby exerting antitumor effects. Moreover, the Vitamin
higher 5-year survival rates than those with lower 25(OH) D metabolite can directly control the expression of multiple
D levels. The Copenhagen City Heart Study, a prospective genes that produce proteins involved in repairing DNA
8
investigation involving 9791 cancer-free participants damage and programmed cell death. This mechanism
at baseline, revealed that diminished Vitamin D levels provides protection against cancer development. Chronic
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13
markedly increased the incidence of HNC. Similarly, a inflammatory responses are crucial in tumorigenesis, and
study based on the European Prospective Investigation Vitamin D may protect against carcinogenesis by inhibiting
into Cancer and Nutrition reported that higher prostaglandin synthesis; inhibiting the p38 MAPK-
Vitamin D levels were strongly linked to a lower HNC mediated proinflammatory signaling pathway, or the
risk. In particular, a doubling in Vitamin D concentration nuclear factor kappa B signaling pathway; and regulating
corresponded to approximately a 30% reduction in HNC the coaction between immune cells and cancer cells to exert
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risk. Given these conflicting findings, a more thorough anti-inflammatory effects. Moreover, Vitamin D induces
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examination of the interaction between Vitamin D levels tumor cell apoptosis by stimulating the endogenous
and HNC risk is required. Vitamin D supplementation apoptotic pathway and can change the autophagic mode of
may reduce HNC risk, as shown in this study, and provides cancer cells from cell survival to cell death. 39,40
new genetic insights into this problem. In a prospective This study had several strengths. First, the MR analysis
cohort study that measured 25(OH)D levels in the Finnish mitigated the disruptions of irrelevant factors and
HNC population before therapy commenced, 25(OH)D reverse causality prevalent in traditional observational
levels were <50 nmoL/L in 65% of the patients, which research. Second, the data used in this study were
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may indicate a connection between Vitamin D and HNC. sourced from the GWAS database, which focuses on
Evidence suggests that Vitamin D is involved in cancer European populations, effectively addressing population
regulation by influencing aspects such as cell proliferation, heterogeneity. MVMR analysis was also employed to
angiogenesis, immune function, and cell metabolism. 9,31,32 control for potential confounders, guaranteeing the
An in vitro study investigating the effects of Vitamin D on validity of the results. Finally, various analysis methods
HNC cells revealed that Vitamin D could inhibit cancer were used, and sensitivity analysis was performed for
cell proliferation, make them prone to apoptosis, and validation.
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increase their sensitivity to chemotherapeutic drugs. However, this study had some limitations. First,
Similarly, in a hamster buccal pouch model, Vitamin D data were derived from a European population, which
inhibited tumorigenesis and growth. In patients with could restrict the applicability of the findings to other
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head-and-neck squamous cell carcinoma (HNSCC), populations. Second, despite performing sensitivity
severe Vitamin D deficiency was related to altered levels of analyses, the possibility of pleiotropy cannot be entirely
immune cell infiltration in and around tumors and impaired excluded, particularly due to biological pleiotropy. Finally,

Volume 9 Issue 2 (2025) 195 doi: 10.36922/ejmo.7099