Serum 25-hydroxyvitamin D levels and risk of lung cancer and histologic types: a Mendelian randomization analysis of the HUNT study

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 randomization (MR) analysis using a prospective cohort study in Norway, including 54580 individuals and 676 incident lung cancer cases. A 25(OH)D allele score was generated based on vitamin D-increasing alleles of rs2282679, rs12785878 and rs10741657. Hazard ratios (HRs) with 95% confidence intervals (CIs) for incidence of lung cancer and histologic types were estimated in relation to the allele score. Inverse-variance weighted method using summarized data of individual single-nucleotide polymorphisms was applied to calculate the MR 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 being 0.99 (95% CI 0.93 to 1.06) per allele score. A 25 nmol/L increase in genetically determined 25(OH)D level was not associated with the incidence of lung cancer overall (MR estimate HR 0.96, 95% CI 0.54 to 1.69) or any histologic type. MR analysis did not suggest causal association between 25(OH)D levels and risk of lung cancer overall or histologic types in this population-based cohort study.