Page 199 - EJMO-9-2

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

survival rate of 40 – 50%. Therefore, an in-depth study on employed as a supplementary method. This approach
5
the factors associated with HNC occurrence is important enabled the concurrent consideration of multiple
for reducing the prevalence of this disease. interrelated exposures and facilitated a more refined
Vitamin D, an essential and versatile lipid-soluble evaluation of the direct influence of specific exposures
vitamin, can be obtained from solar exposure and dietary on the outcome by controlling for confounding factors
22
sources. 25-hydroxyvitamin D (25(OH)D), a stable related to other exposures. Using this approach, we
Vitamin D metabolite, is acknowledged as a dependable successfully eliminated confounding due to known
indicator for assessing Vitamin D levels in the body. confounders, resulting in a more precise assessment of
6
Vitamin D is critical for maintaining optimal, and its the causality of Vitamin D for HNC risk.
deficiency is closely linked to several diseases such as 2. Materials and methods
cardiovascular disorders, COVID-19, bone diseases,
diabetes, and autoimmune diseases. In addition, 2.1. Study design
7
considerable attention has been directed toward the Univariate and multivariate MR methods were employed
relationship between vitamins and cancer incidence. in this study. Vitamin D levels were treated as the exposure
Studies have shown that Vitamin D can affect particular variable, and HNC served as the outcome of interest.
cellular signaling pathways involved in tumor growth, Single-nucleotide polymorphisms (SNPs), used as IVs,
consequently controlling the apoptosis, differentiation, were strongly linked to Vitamin D levels. Moreover, to
and metastasis of tumor cells. A meta-analysis indicated accurately assess the direct influence of Vitamin D on
8,9
that high Vitamin D levels correlate with a decrease in increasing HNC risk, certain adjustments were made
cancer incidence and mortality. A randomized study in the MVMR analysis to account for the influence of
10
indicated that increasing Vitamin D levels markedly two important factors, that is, smoking and alcohol
reduced cancer risk in postmenopausal women. In consumption. This was performed to exclude any possible
11
particular, when examining the causality of Vitamin D for bias attributed to these factors. MR analyses must adhere to
HNC risk, certain studies present evidence that Vitamin three basic assumptions (Figure 1): (1) the IVs are strongly
D decreases HNC risk. 5,12-14 However, some studies have linked to the exposures, (2) the IVs are not related to any
failed to identify a noteworthy connection between the confounders, (3) and the IVs influence the outcomes only
two. To overcome the challenges of confounding and through the exposures and are not influenced by other
15
reverse causality prevalent in traditional observational pathways.
studies and elucidate the causal association between
Vitamin D and HNC risk, this study employed Mendelian 2.2. Data sources
randomization (MR) to investigate this potential causality The IEU OPEAN GWAS PROJECT database provided the
more thoroughly. data for this study. The dataset for Vitamin D levels (ebi-

Using genetic variation as an instrumental variable a-GCST005367) used in the genome-wide association
(IV), MR can investigate the factors that influence study (GWAS) was derived from the study by Jiang et al.
disease exposure. This approach utilizes the random which contained a total of 79,366 samples and 2,538,249
16
assignment of alleles during fertilization, similar to the SNPs. The HNC dataset (ieu-b-4912 was obtained
23
randomization employed in randomized controlled from the UK Biobank, which involved 1106 patients and
trials. Because genetic variations remain stable during an 372,016 controls. Data on ever-smoking (ieu-b-4858) and
17
individual’s life, independent of lifestyle, environmental alcohol consumption (ieu-b-4834) were extracted from
factors, and other potential confounders, MR studies
effectively mitigate confounding bias and reverse
causation problems that are prevalent in traditional
observational studies. This approach provides reliable
18
and accurate causal inferences for understanding
disease risk factors. In addition, other MR studies have
explored the association of Vitamin D with conditions
such as lung disease, cardiovascular disease, and certain
cancers, confirming the feasibility of this approach. 19-21
This study employed a two-sample MR approach to
examine the causal link between Vitamin D levels and
HNC. To ensure that our analytical results were accurate
and robust, multivariate MR (MVMR) analysis was also Figure 1. Core assumptions of Mendelian randomization

Volume 9 Issue 2 (2025) 191 doi: 10.36922/ejmo.7099