ArticleCancer causes & control : CCC2026
Genetically predicted vitamin D levels and risk of head and neck cancer: a mendelian randomization study.
Article in Cancer causes & control : CCC, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesObservational studies examining the association between vitamin D and head and neck cancer (HNC) have reported conflicting results. We conducted a two-sample MR study to investigate the causal association between genetically predicted serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of HNC and its major subtypes: oral cavity, laryngeal, hypopharyngeal, and HPV-negative oropharyngeal cancers.
designGenetic instruments were selected from GWAS of 441,291 individuals (UK Biobank). Cancer outcomes were obtained from the HEADSpAcE consortium. Multiple sclerosis (MS) was analyzed as a positive control. We identified 115 independent genetic instruments for serum 25(OH)D. Causal estimates were primarily derived using inverse variance weighted (IVW) MR, supported by MR-Egger, weighted median, and mode-based methods. Extensive sensitivity analyses assessed heterogeneity, pleiotropy, and directionality.
resultsWe identified 115 independent genetic instruments for serum 25(OH)D levels, which explained 5.12% of the total phenotypic variance. The mean F-statistic was 198.3 and satisfied MR assumptions. Only 17 of 682 (2.5%) SNP-confounder associations reached nominal significance (p < 5 × 10⁻
conclusionsThis study provides robust genetic evidence that circulating 25(OH)D levels are not a major causal determinant of HNC risk and that our instruments are not confounded by major lifestyle or UV-related factors.
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