Abstract
Objective
Vitamin D and its receptor (VDR) involve in multiple cellular processes and play an important role in the initiation and progression of malignancy. Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms (SNPs) in VDR may be of prognostic significance in non-small cell lung cancer (NSCLC).
Methods
We examined plasma 25-hydroxyvitamin D [25(OH)D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay (ELISA) and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform.
Results
Patients with higher plasma 25(OH)D levels had worse survival than patients with lower ones (P for trend = 0.048). The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival (adjusted HR = 1.61, 95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51, 95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG). A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased (P for trend = 0.003). There were no significant associations between VDR polymorphisms and plasma 25(OH)D levels.
Conclusion
Our findings indicate that plasma 25(OH)D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74–108.
Gönen M, Weiser MR. Whither TNM? Semin Oncol 2010; 37:27–30.
Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005; 5:845–856.
Kulie T, Groff A, Redmer J, et al. Vitamin D: an evidence-based review. J Am Board Fam Med 2 2009; 22:698–706
Ali MM, Vaidya V. Vitamin D and cancer. J Cancer Res Ther 2007; 3:225–230.
Srinivasan M, Parwani AV, Hershberger PA, et al. Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer. J Steroid Biochem Mol Biol 2011; 123:30–36
Güzey M, Sattler C, DeLuca HF. Combinational effects of vitamin D3 and retinoic acid (all trans and 9 cis) on proliferation, differentiation, and programmed cell death in two small cell lung carcinoma cell lines. Biochem Biophys Res Commun 1998; 249:735–744.
Freedman DM, Looker AC, Abnet CC, et al. Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988-2006). Cancer Res 2010; 70:8587–8589
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116:281–297.
Obi-Tabot ET, Tian XQ, Chen TC, et al. A human skin equivalent model that mimics the photoproduction of vitamin D3 in human skin. In Vitro Cell Dev Biol Anim 2000; 36:201–204
Torres C, de la Torre MS, Garcia-Moruja C, et al. Immunophenotype of Vitamin D Receptor Polymorphism Associated to Risk of HIV-1 Infection and Rate of Disease Progression. Curr HIV Res 2010; 8:487–489
Uitterlinden AG, Fang Y, Van Meurs JB, et al. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004; 338:143–156.
Arai H, Miyamoto KI, Yoshida M, et al. The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. J Bone Miner Res 2001; 16:1256–1256
Zhou W, Heist RS, Liu G, et al. Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev 2006; 15:2239–2234
Heist RS, Zhou W, Wang Z, et al. Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. J Clin Oncol 2008; 26:5596–5596
Lundin AC, Söderkvist P, Eriksson B, et al. Association of breast cancer progression with a vitamin D receptor gene polymorphism. South-East Sweden Breast Cancer Group. Cancer Res 1999; 59:2332–2334
Huang SP, Huang CY, Wu WJ, et al. Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy. Int J Cancer 2006; 119:1902–1907.
Hu Z, Wang H, Shao M, et al. Genetic variants in MGMT and risk of lung cancer in Southeastern Chinese: a haplotype-based analysis. Hum Mutat 2007; 28:431–440
Ng K, Meyerhardt JA, Wu K, et al. Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. J Clin Oncol 2008; 26:2984–2991
Tamez S, Norizoe C, Ochiai K, et al. Vitamin D receptor polymorphisms and prognosis of patients with epithelial ovarian cancer. Br J Cancer 2009; 101:1957–1960.
Zhang M, Hu Z, Huang J, et al. A 3′-untranslated region polymorphism in IGF1 predicts survival of non-small cell lung cancer in a Chinese population. Clin Cancer Res 2010; 16:1236–1234
Goodwin PJ, Ennis M, Pritchard KI, et al. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol 2009; 27:3757–3763
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported in part by Key Grant of the National Natural Science Foundation of Chian (No. 30730080), National Natural Science Foundation of China (No. 30972541, 30901233), National Outstanding Youth Science Foundation of Chian (No. 30425001), and Key Laboratory of Laboratory Mecicine of Jiangsu Province (No. XK200731).
Contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liu, Y., Chen, W., Hu, Zb. et al. Plasma vitamin D levels and vitamin D receptor polymorphisms are associated with survival of non-small cell lung cancer. Chin. J. Cancer Res. 23, 33–37 (2011). https://doi.org/10.1007/s11670-011-0033-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11670-011-0033-3