# Genetically predicted vitamins supplementation and risk of skin cancers: a Mendelian randomization study

## TL;DR

This study finds that genetically predicted folate supplementation is linked to a lower risk of melanoma, suggesting it could help prevent this skin cancer.

## Contribution

The study provides novel evidence using Mendelian randomization to show a causal link between folate supplementation and reduced melanoma risk.

## Key findings

- Folate supplementation was associated with a reduced melanoma risk (IVW OR = 0.88; 95% CI 0.80–0.96; P = 0.006).
- No significant associations were found between vitamins A, B6, B12, C, D, E and skin cancers.
- MRlap and sensitivity analyses confirmed the robustness of the folate-melanoma inverse relationship.

## Abstract

The causal relationship between vitamins supplementation and the risk of skin cancers remains unclear. We conducted a Mendelian randomization study to assess the associations between vitamins supplementation and skin cancers in the general population.

We aimed to investigate the causal relationship of vitamins (A-E) supplementation with skin cancers using and utilizing the linkage disequilibrium score regression (LDSC) Mendelian randomization (MR).

We selected genome-wide significant single-nucleotide polymorphisms (SNPs) linked to vitamin supplements (A-E). Summary-level data for melanoma, basal cell carcinoma, and squamous cell carcinoma were obtained from large-scale genome-wide association studies. We applied the inverse-variance weighted (IVW) method within a random effects model, alongside weighted median, MR-Egger, simple median, sensitivity analyses, and MRlap methods to ensure robustness. A meta-analysis was conducted to assess the causal relationship between vitamins supplementation and melanoma. The STROBE-MR checklist was followed throughout.

Folate supplementation was associated with a reduced melanoma risk (IVW OR = 0.88; 95% CI 0.80–0.96; P = 0.006). The MR analysis indicated a significant inverse causal relationship. Heterogeneity and sensitivity analyses confirmed minimal impact from individual SNPs. MRlap corrected for potential estimation bias due to sample overlap, which was not significant, reinforcing the IVW findings. The meta-analysis ensured robust and stable results. LDSC regression analysis suggests a weak causal relationship between folate supplementation and melanoma. Yet no association was found between genetically predicted vitamins A, B6, B12, C, D, E, and skin cancers.

Both observational meta-analysis and MR analysis based on genetic variation provide robust evidence indicat that folate supplementation decreases the risk of melanoma, suggesting that interventions targeting folate supplementation may contribute to the primary prevention of melanoma. Further studies are needed to explore the potential association between other vitamins supplementation and the risk of skin cancers.

The online version contains supplementary material available at 10.1007/s12672-025-01905-9.