Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient–nutrient interaction
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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.
KeywordsSerum 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.
- 5.Turner A, McGowan L, Millen A, et al. (2012) Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology. Eur Respir J. doi: 10.1183/09031936.00002912
- 10.Haussler MR, Haussler CA, Jurutka PW, et al. (1997) The vitamin D hormone and its nuclear receptor: molecular actions and disease states. The Journal of Endocrinology. 154 (Suppl): S57-73–S57-73Google Scholar
- 11.Zou A, Elgort MG, Allegretto EA (1997) Retinoid X receptor (RXR) ligands activate the human 25-hydroxyvitamin D3–24-hydroxylase promoter via RXR heterodimer binding to two vitamin D-responsive elements and elicit additive effects with 1,25-dihydroxyvitamin D3. J Biol Chem 272:19027–19034PubMedCrossRefGoogle Scholar
- 12.Arnhold T, Tzimas G, Wittfoht W, Plonait S, Nau H. (1996) Identification of 9-cis-retinoic acid, 9,13-di-cis-retinoic acid, and 14-hydroxy-4,14-retro-retinol in human plasma after liver consumption. Life Sci 59: PL169–77Google Scholar
- 23.Gunter EW, Lewis BG, Koncikowski SM (1996) Laboratory procedures used for the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994Google Scholar
- 29.IOM (Institute of Medicine) (2011) Overview of Vitamin D. Dietary Reference Intake for Calcium and Vitamin D. Washington, DC: The National Academics PressGoogle Scholar