Serum 25-Hydroxyvitamin D and Risk of Lung Cancer in Male Smokers: A Nested Case-Control Study

Background: A role for vitamin D in cancer risk reduction has been hypothesized, but few data exist for lung cancer. We investigated the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25(OH)D], and lung cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers. Methods: Lung cancer cases (n = 500) were randomly selected based on month of blood collection, and 500 controls were matched to them based on age and blood collection date. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using multivariate-adjusted conditional logistic regression. To account for seasonal variation in 25(OH)D concentrations, season-specific and season-standardized quintiles of 25(OH)D were examined, and models were also stratified on season of blood collection (darker season =November–April and sunnier season =May–October). Pre-determined, clinically-defined cutpoints for 25(OH)D and 25(OH)D as a continuous measure were also examined. Results: Overall, 25(OH)D was not associated with lung cancer. Risks were 1.08 (95 % CI 0.67–1.75) and 0.83 (95 % CI 0.53– 1.31) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.91 (95 % CI 0.48–1.72) for the $75 vs.,25 nmol/L clinical categories. Inverse associations were, however, suggested for subjects with blood collections from November–April, with ORs of 0.77 (95 % CI 0.41–1.45, p-trend = 0.05) and 0.65 (95 % CI 0.37–1.14, p