MR shows high serum 25(OH)D levels reduce laryngeal cancer risk.

GWAS suggests vitamin D may have a protective role against laryngeal cancer.

Vit D deficiency linked to higher laryngeal cancer risk, suggesting preventive.

The levels of vitamin D in the human body are primarily measured through serum 25-hydroxyvitamin D (25(OH)D) levels. Observational studies suggest a potential association between the incidence of laryngeal cancer and vitamin D levels, but the causality remains unclear. This study aims to investigate the potential causal relationship between vitamin D levels and laryngeal cancer.

This Mendelian Randomization (MR) study is based on large-scale GWAS (Genome-Wide Association Study) summary datasets. We selected two different datasets of 25(OH)D and conducted two two-sample univariable Mendelian Randomization (MR) analyses. Four different MR methods were applied, and a series of sensitivity analyses were performed. In addition, a two-sample Mendelian randomization was conducted to account for the confounding effect of smoking. Furthermore, we performed GO enrichment analyses on the SNPs used as instrumental variables.

The combined findings from both univariable MR analyses support a potential causal relationship between serum 25(OH)D levels and laryngeal cancer, suggesting that higher levels of vitamin D may have a protective effect against laryngeal cancer. Multivariable MR analysis showed that even after accounting for smoking as a confounding factor, the impact of 25(OH)D on laryngeal cancer remained significant. Enrichment analysis further indicated that 25(OH)D may inhibit the occurrence and progression of laryngeal cancer by regulating the metabolism of exogenous substances, lipid metabolism, and cellular responses to environmental stimuli.

Higher serum 25-hydroxyvitamin D levels serve as a protective factor against laryngeal cancer, suggesting that increasing vitamin D levels may reduce the risk of laryngeal cancer.

This was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.

Serum 25-hydroxyvitamin D level

Laryngeal cancer

Genome-wide association study

Mendelian randomization

Single nucleotide polymorphism

© 2025 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España, S.L.U.