title: Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient-nutrient interaction.
abstract: OBJECTIVE
  Excess vitamin A may interrupt vitamin D-mediated transcription of target genes. This study investigated whether serum 25-hydroxyvitamin D [25(OH)D] concentrations were associated with lung cancer mortality, and whether this association varied by excess circulating vitamin A and vitamin A/β-carotene supplement use.
  
  
  METHODS
  We analyzed 16,693 men and women in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Lung cancer mortality (n = 258, 104 were former smokers and 23 were never smokers) were identified through National Death Index as of 2006. Serum 25(OH)D was measured by a radioimmunoassay. Vitamin A biomarkers including serum retinol, β-carotene, and retinyl esters were measured by HPLC. Supplement use for the past month was obtained by self-report. Multivariate-adjusted hazard ratios (HR) were estimated by Cox proportional hazard models.
  
  
  RESULTS
  There was no association of serum 25(OH)D with overall lung cancer mortality. Among nonsmokers, ≥44 vs. <44 nmol/L of serum 25(OH)D was associated with a decreased risk (HR = 0.53, 95 % CI = 0.31-0.92, former/never smokers and HR = 0.31, 95 % CI = 0.13-0.77, distant-former [quit ≥20 years]/never smokers). The associations were not observed among participants with excess circulating vitamin A (serum retinyl esters ≥7.0 μg/dL or the ratio of retinyl esters to retinol ≥0.08) or vitamin A/β-carotene supplement users. However, statistical evidence to support effect modification of vitamin A was less clear.
  
  
  CONCLUSIONS
  Serum 25(OH)D concentrations were inversely associated with lung cancer mortality in nonsmokers. The beneficial association was diminished among those with excess circulating vitamin A or vitamin A/β-carotene supplement users.
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4B402, Seattle, WA 98109-1024, USA. tcheng@fhcrc.org
authors: Ting-Yuan David
authors: TY
authors: Cheng
authors: Marian L
authors: ML
authors: Neuhouser
mesh_terms: D000328:Adult; D019587:Dietary Supplements / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D018565:Food-Drug Interactions; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D016016:Proportional Hazards Models; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014801:Vitamin A / Q000097:blood*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D019207:beta Carotene / Q000097:blood
chemical_list: D019207:beta Carotene; D014801:Vitamin A; D014807:Vitamin D; C104450:25-hydroxyvitamin D