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Mendelian Randomization Analysis reveals Inverse Genetic Risks between Skin Cancers and Vitiligo.

ABSTRACT: Several observational studies have demonstrated a consistent pattern of decreased melanoma risk among patients with vitiligo. More recently, this finding has been supported by a suggested genetic relationship between the two entities, with certain variants significantly associated with an increased risk of melanoma, basal cell carcinoma, and squamous cell carcinoma but a decreased risk of vitiligo. We compared 48 associated variants from a recently published GWAS and identified three variants-located in the TYR, MC1R-DEF8, and RALY-EIF2S2-ASIP-AHCY-ITCH loci- that correlated with an increased risk for melanoma, basal cell carcinoma, and squamous cell carcinoma and a decreased risk for vitiligo. We then used results of skin cancers and vitiligo GWAS to compare the shared genetic properties between these two traits through an unbiased Mendelian randomization analysis. Our results suggest that the inverse genetic relationship between common skin cancers and vitiligo is broader than previously reported owing to the influence of shared genome-wide significant associations.

SUBMITTER: Rashid S

PROVIDER: S-EPMC10685305 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Mendelian Randomization Analysis reveals Inverse Genetic Risks between Skin Cancers and Vitiligo.

Rashid Sarem S Molotkov Ivan I Klebanov Nikolai N Shaughnessy Michael M Daly Mark J MJ Artomov Mykyta M Tsao Hensin H

JID innovations : skin science from molecules to population health 20230708 6

Several observational studies have demonstrated a consistent pattern of decreased melanoma risk among patients with vitiligo. More recently, this finding has been supported by a suggested genetic relationship between the two entities, with certain variants significantly associated with an increased risk of melanoma, basal cell carcinoma, and squamous cell carcinoma but a decreased risk of vitiligo. We compared 48 associated variants from a recently published GWAS and identified three variants-lo ...[more]

PMID: 38034848

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Project description:BackgroundThe 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.ObjectiveWe 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).Materials and methodsWe 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.ResultsFolate 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.ConclusionBoth 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.

Dataset Information

Mendelian Randomization Analysis reveals Inverse Genetic Risks between Skin Cancers and Vitiligo.

Publications

Mendelian Randomization Analysis reveals Inverse Genetic Risks between Skin Cancers and Vitiligo.

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