Cancer Causes & Control

, Volume 23, Issue 9, pp 1557–1565 | Cite as

Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient–nutrient interaction

  • Ting-Yuan David ChengEmail author
  • Marian L. Neuhouser
Original paper



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.


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.


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.


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.


Serum 25-hydroxyvitamin D Retinol Retinyl esters Lung cancer The Third National Health and Nutrition Examination Survey (NHANES III) 



Funding for this work was provided by the Fred Hutchinson Cancer Research Center, Seattle, WA.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2012_33_MOESM1_ESM.doc (37 kb)
Supplementary material 1 (DOC 37 kb)


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Ting-Yuan David Cheng
    • 1
    • 2
    Email author
  • Marian L. Neuhouser
    • 1
    • 2
  1. 1.Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of EpidemiologyUniversity of WashingtonSeattleUSA

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