Abstract
We aimed to investigate potential causal associations between serum 25-hydroxyvitamin D (25(OH)D) levels and incidence of lung cancer overall and histologic types.We performed a Mendelian randomisation analysis using a prospective cohort study in Norway, including 54 580 individuals and 676 incident lung cancer cases. A 25(OH)D allele score was generated based on the vitamin D-increasing alleles rs2282679, rs12785878 and rs10741657. Hazard ratios with 95% confidence intervals for incidence of lung cancer and histologic types were estimated in relation to the allele score. The inverse-variance weighted method using summarised data of individual single nucleotide polymorphisms was applied to calculate the Mendelian randomisation estimates.The allele score accounted for 3.4% of the variation in serum 25(OH)D levels. There was no association between the allele score and lung cancer incidence overall, with HR 0.99 (95% CI 0.93-1.06) per allele score. A 25 nmol·L(-1) increase in genetically determined 25(OH)D level was not associated with the incidence of lung cancer overall (Mendelian randomisation estimate HR 0.96, 95% CI 0.54-1.69) or any histologic type.Mendelian randomisation analysis did not suggest a causal association between 25(OH)D levels and risk of lung cancer overall or histologic types in this population-based cohort study.