Associations of serum 25-hydroxyvitamin D level with incidence of lung cancer and histologic types in Norwegian adults: a case-cohort analysis of the HUNT study

Background: Previous prospective studies have shown inconsistent associations between serum 25-hydroxyvitamin D [25(OH)D] level and lung cancer incidence. The aim of the present study was to explore the associations of serum 25(OH)D levels with incidence of lung cancer overall and different histologic types. Methods: We performed a population-based prospective case-cohort study including 696 incident lung cancer cases and 5804 individuals in a subcohort who participated in the second survey of the Nord-Trøndelag Health Study in Norway. Cox proportional hazards regression models counting for the case-cohort design were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for lung cancer overall or histologic types in relation to serum 25(OH)D levels. Results: Compared with the 4th season-specific quartile of 25(OH)D (median 68.0 nmol/L), lower 25(OH)D levels were not associated with the incidence of overall, small or squamous cell lung cancer. However, the risk of adenocarcinoma was lower in the 2nd and 3rd quartiles (median 39.9 and 51.5 nmol/L) compared with the 4th quartile, with HRs of 0.63 (95% CI 0.41 to 0.98) and 0.58 (0.38 to 0.88), respectively. The associations of lower levels of 25(OH)D with a reduced risk of adenocarcinoma were only observed in the overweight/obese subjects [HRs for 2nd and 3rd quartiles: 0.40 (0.22 to 0.72) and 0.50 (0.27 to 0.92)] but not in the normal weight subjects [HRs: 0.95 (0.52 to 1.75) and 0.60 (0.32 to 1.10)]. Conclusions: Serum 25(OH)D levels were not associated with the risk of lung cancer in general. The observation that lower 25(OH)D levels were associated with a lower risk of adenocarcinoma should be interpreted with caution. This is a pre-print of an article published in [European Journal of Epidemiology]. The final authenticated version is available online at: https://doi.org/10.1007/s10654-017-0324-1