Clinical Significance of Serum 25-Hydroxyvitamin D Levels in Non-Small Cell Lung Cancer
Objectives: Lung cancer is the most common cause of cancer-related deaths worldwide. The use of tobacco and tobacco products is among the leading risk factors with proven association with lung cancer, although various environmental and dietary factors have been also implicated. Vitamin D deficiency has been identified as a poor prognostic factor in advanced stage colon cancer and breast cancer. The aim of the present study was to compare 25-hydroxyvitamin D [25(OH)D] levels between patients with non-small cell lung cancer (NSCLC) at the time of diagnosis and healthy controls and to evaluate the differences in serum 25(OH)D levels across the subgroups and stages of NSCLC. Methods: A total of 462 patients with NSCLC who were followed and treated in three participating centers were compared retrospectively with and age- and sex-matched 462 healthy controls who underwent testing for serum calcium, lactate dehydrogenase (LDH), magnesium, phosphorus, creatinine, and vitamin D levels in the between January 2016 and June 2018. The patients with NSCLC were further classified according to the histological subtype. Results: The mean age was 63.46±8.86 years. The patient group was composed of 58 females (12.6%) and 404 males (87.4%). Serum 25(OH)D, calcium, LDH, and magnesium levels were significantly different between the patient and the control group (p=0.0001, p=0.0001, p=0.0001, p=0.0001, respectively). Among patients with NSCLC, serum 25(OH) D was significantly lower in patients with adenocarcinoma subtype than in patients with squamous-cell carcinoma subtype (p=0.001). There was a significant correlation between advanced stage with decreased serum 25(OH)D and increased LDH levels (p=0.0001, p=0.0001, respectively). Conclusion: The study is the most extensive study in our region in terms of the number of participating patients. Demonstration of a difference in serum 25(OH)D levels between histological subtypes also contributes to the literature.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87– 108.
2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008;83:584–94. [CrossRef]
3. Liu W, Zhang L, Xu HJ, Li Y, Hu CM, Yang JY, et al. The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis. Int J Mol Sci 2018 Sep 13 [E-pub ahead of print], doi: 10.3390/ ijms19092736. [CrossRef]
4. Han Y, Zhang Y, Jia T, Sun Y. Molecular mechanism underlying the tumor-promoting functions of carcinoma-associated fibroblasts. Tumour Biol 2015;36:1385–94. [CrossRef]
5. Grant WB. 25-hydroxyvitamin D and breast cancer, colorectal cancer, and colorectal adenomas: case-control versus nested case-control studies. Anticancer Res 2015;35:1153–60.
6. Zhou W, Suk R, Liu G, Park S, Neuberg DS, Wain JC, et al. Vitamin D is associated with improved survival in early-stage nonsmall cell lung cancer patients. Cancer Epidemiol Biomarkers Prev 2005;14:2303–9. [CrossRef]
7. Zhou W, Heist RS, Liu G, Asomaning K, Neuberg DS, Hollis BW, et al. Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients. J Clin Oncol 2007;25:479–85. [CrossRef]
8. Cheng TY, Neuhouser ML. Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient-nutrient interaction. Cancer Causes Control 2012;23:1557–65. [CrossRef]
9. Nakagawa K, Kawaura A, Kato S, Takeda E, Okano T. 1 alpha,25-Dihydroxyvitamin D(3) is a preventive factor in the metastasis of lung cancer. Carcinogenesis 2005;26:429–40.
10. Nakagawa K, Sasaki Y, Kato S, Kubodera N, Okano T. 22-Oxa-1alpha,25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer. Carcinogenesis 2005;26:1044–54.
11. Hershberger PA, Modzelewski RA, Shurin ZR, Rueger RM, Trump DL, Johnson CS. 1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and downmodulates p21(Waf1/Cip1) in vitro and in vivo. Cancer Res 1999;59:2644–9.
12. Skaaby T, Husemoen LL, Thuesen BH, Pisinger C, Jørgensen T, Fenger RV, et al. Vitamin D status and chronic obstructive pulmonary disease: a prospective general population study. PLoS One 2014;9:e90654. [CrossRef]
13. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 2011;128:1414–24. [CrossRef]
14. Zhang L, Wang S, Che X, Li X. Vitamin D and lung cancer risk: a comprehensive review and meta-analysis. Cell Physiol Biochem 2015;36:299–305. [CrossRef]
15. Liu J, Dong Y, Lu C, Wang Y, Peng L, Jiang M, et al. Meta-analysis of the correlation between vitamin D and lung cancer risk and outcomes. Oncotarget 2017;8:81040–51. [CrossRef]
16. Muller DC, Hodge AM, Fanidi A, Albanes D, Mai XM, Shu XO, et al. No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3). Ann Oncol 2018;29:1468–75.
17. Higashimoto Y, Ohata M, Nishio K, Iwamoto Y, Fujimo-to H, Uetani K, et al. 1 alpha, 25-dihydroxyvitamin D3 and all-trans-retinoic acid inhibit the growth of a lung cancer cell line. Anticancer Res 1996;16:2653–9.
18. Mazzilli SA, Hershberger PA, Reid ME, Bogner PN, Atwood K, Trump DL, et al. Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model. Cancer Prev Res (Phila) 2015;8:895–904. [CrossRef]
19. Hirsch FR, Spreafico A, Novello S, Wood MD, Simms L, Papotti M.The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review. J Thorac Oncol 2008;3:1468–81. [CrossRef]
20. Wang X, Cui J, Gu J, He H, Li B, LiW. Plasma 25-hydroxyvitamin D deficiency is associated with the risk of non-small cell lung cancer in a Chinese population. Cancer Biomark 2015;15:663–8.
21. Akiba T, Morikawa T, Odaka M, Nakada T, Kamiya N, Ya-mashita M, et al. Vitamin D Supplementation and Survival of Patients with Non-small Cell Lung Cancer: A Random-ized, Double-Blind, Placebo-Controlled Trial. Clin Cancer Res 2018;24:4089–97. [CrossRef]
22. Feng Q, Zhang H, Dong Z, Zhou Y, Ma J. Circulating 25-hydroxyvitamin D and lung cancer risk and survival: A dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore) 2017;96:e8613. [CrossRef]