Serum 25-hydroxyvitamin D levels and risk of lung cancer and histologic types: A Mendenlian randomization analysis of the Hunt study

Abstract

Summary Background Meta-analysis of observational studies have suggested an inverse association between serum 25-hydroxyvitamin D [25(OH)D] levels and lung cancer incidence. The aim of the current study was to explore if there were causal associations between serum 25(OH)D levels and incidence of lung cancer overall and different histologic types. Methods We performed a Mendelian randomization (MR) analysis using data from a 19-year population-based 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 number of vitamin D-increasing alleles of rs2282679, rs12785878 and rs10741657, and was used as an instrumental variable. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incidence of lung cancer and histologic types in relation to the allele score. Inverse-variance weighted method using summarized data of individual SNPs were applied to calculate the MR estimates. Results The allele score accounted for 3.4% of the variation of serum 25(OH)D levels. There were no associations 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). The allele score and genetically determined 25(OH)D were not significantly associated with any histologic types of lung cancer. Conclusions MR analysis suggested that there were no causal associations between 25(OH)D levels and risks of lung cancer and histologic types in a homogeneous population-based prospective cohort study.