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Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

  • Atoum, Manar Fayiz (Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Hashemite University) ;
  • Tchoporyan, Melya Nizar (Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Hashemite University)
  • Published : 2014.09.15

Abstract

Background: The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form $1,25(OH)_2D$ to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study wass to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. Materials and Methods: This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by paired t-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. Results: The vitamin D serum level was significantly lower among colorectal cancer patients (8.34 ng/ml) compared to the healthy control group (21.02ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT ($8.91{\pm}4.31$) and Tt ($9.15{\pm}5.25$) genotypes compared to control ($21.3{\pm}8.31$) and ($19.3{\pm}7.68$); respectively. Conclusions: There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment.

Keywords

Colorectal cancer;vitamin D receptor;gene polymorphism;vitamin D

References

  1. Ashktorab H, Nguza B, Fatemi M, et al (2011). Case-control study of vitamin D, dickkopfhomolog 1 (DKK1) gene methylation, VDR gene polymorphism and the risk of colon adenoma in african americans. PLoS One, 6, 25314. https://doi.org/10.1371/journal.pone.0025314
  2. Bai YH, Lu H, Hong D, et al (2012). Vitamin D receptor gene polymorphisms and colorectal cancer risk:a systematic metaanalysis. World J Gastroenterol, 18, 1672-9. https://doi.org/10.3748/wjg.v18.i14.1672
  3. Biancuzzo RM, Clarke N, Reitz RE, Travison TG, Holick M.F (2013). Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation. J Clin Endocrinol Metab, 98, 973-9. https://doi.org/10.1210/jc.2012-2114
  4. Bid HK, Mishra DK, Mittal RD (2005). Vitamin-D receptor (VDR) gene (Fok1, Taq1 and Apa1) polymorphisms in healthy individuals from north Indian population. Asian Pac J Cancer Prev, 6, 147-52.
  5. Bhanushali AA, Lajpal N, Kulkarni SS, et al (2009). Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels. Indian J Hum Genet, 15, 108-13. https://doi.org/10.4103/0971-6866.60186
  6. Bouillon R, Carmeliet G, Verlinden L, et al (2008).Vitamin D and human health: lessons from vitamin D receptor null mice. Endocrine reviews, 29, 726-76. https://doi.org/10.1210/er.2008-0004
  7. Deeb KK, Trump DL, Johnson CS (2007). Vitamin D signaling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer, 7, 684-700. https://doi.org/10.1038/nrc2196
  8. Byers SW, Rowlands T, Beildeck M, Bong YS (2012). Mechanism of action of vitamin D and the vitamin D receptor in colorectal cancer prevention and treatment. Rev Endocr Metab Disord, 13, 31-8. https://doi.org/10.1007/s11154-011-9196-y
  9. Carlberg C (2003). Current understanding of the function of the nuclear vitamin D receptor in response to its natural and synthetic ligands. Recent Results Cancer Res, 164, 29-42. https://doi.org/10.1007/978-3-642-55580-0_2
  10. Carlberg C, Seuter S (2009). A genomic perspective on vitamin D signaling. Anticancer Res, 29, 3485-93.
  11. Cunningham D, Atkin W, Lenz HJ, et al (2010). Colorectal cancer. The Lancet, 375, 1030-47. https://doi.org/10.1016/S0140-6736(10)60353-4
  12. Dilmec F, Ozgonul A, Akkafa F, (2009). Determination of ApaI and TaqI polymorphisms of VDR gene in a group of Turkish patients with colorectal cancer. Internat J Hematol Oncol, 19, 18-22.
  13. Freedman DM, Looker AC, Chang SC, Graubard BI. (2007). Prospective study of serum vitamin D and cancer mortality in the United States. J Nat Cancer Inst, 99, 1594-602. https://doi.org/10.1093/jnci/djm204
  14. Gunduz M, Cacyna C, Toptas B, et al (2012). Association of vitamin D receptor gene polymorphisms with colon cancer. Genet Test Mol Biomarkers, 16,1058-61. https://doi.org/10.1089/gtmb.2012.0044
  15. Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR (2006). Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol, 57, 234-40. https://doi.org/10.1007/s00280-005-0059-7
  16. Arai H, Miyamoto KI, Yoshida M, et al (2001). The polymorphism in the caudal-related hemodomain protein Cdx-2 binding elements in the human vitamin D receptor gene. J Bone Miner Res, 16, 1256-64. https://doi.org/10.1359/jbmr.2001.16.7.1256
  17. Haussler MR, Jurutka PW, Mizwicki M, Norman AW (2011).Vitamin D receptor (VDR)-mediated actions of $1\alpha$,25(OH)2vitamin D3: Genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab, 25, 543-59. https://doi.org/10.1016/j.beem.2011.05.010
  18. Flugge J, Krusekopf S, Goldammer M, et al (2007). Vitamin D receptor haplotypes protect against development of colorectal cancer. Eur J Clin Pharmacol, 63, 997-1005. https://doi.org/10.1007/s00228-007-0367-4
  19. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al (2011). Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 96, 1911-30. https://doi.org/10.1210/jc.2011-0385
  20. Ingles SA, Ross RK, Yu MC, et al (1997). Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Nat Cancer Inst, 89,166-70 https://doi.org/10.1093/jnci/89.2.166
  21. Jenab M, Bueno-de-Mesquita HB, Ferrari P, et al (2010). Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study. BMJ, 340, 5500. https://doi.org/10.1136/bmj.b5500
  22. Jehan F, d'Alesio A, Garabedian M (2007). Exons and functional regions of the human vitamin D receptor gene around and within the main 1a promoter are well conserved among mammals. J Steroid Biochem Mol Boil, 103, 361-7. https://doi.org/10.1016/j.jsbmb.2006.12.057
  23. Jones G (2008). Pharmacokinetics of vitamin D toxicity. American J Clin Nutr, 88, 582-6.
  24. Jordan Cancer Registry, Cancer Incidence In Jordan 2010.
  25. Kang K, Lee S, Jeon E, et al (2011). Emerging role of vitamin D in colorectal cancer. World J Gastrointest Oncol, 3, 123-7.
  26. Kostner K, Denzer N, Muller CS, et al (2009). The Relevance of vitamin D receptor gene polymorphisms for cancer: a review of literature. Anticancer Research, 29, 3511-36.
  27. Labianca R, Nordlinger B, Beretta GD, Brouquet A, Cervantes A (2010). Guidelines working group "Primary colon cancer: ESMO clinical practice guidelines for diagnosis, adjuvant treatment and follow-up". Ann Oncol, 21, 70-7. https://doi.org/10.1093/annonc/mdq168
  28. Larriba MJ, Munoz A (2005). SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications. Br J Cancer, 92, 985-9. https://doi.org/10.1038/sj.bjc.6602484
  29. Lee JE, Li H, Chan AT, et al (2011). Circulatory levels of vitamin D and colon and rectal cancer: Physicians health study and a meta-analysis of prospective studies. Cancer Prev Res, 4, 735-43. https://doi.org/10.1158/1940-6207.CAPR-10-0289
  30. Lips P (2007).Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol, 103, 620-5. https://doi.org/10.1016/j.jsbmb.2006.12.076
  31. Mallah EM, Arafat TA, Hamad MF, et al (2011). Plasma concentrations of 25-hydroxyvitamin D among Jordanians: Effect of biological and habitual factors on vitamin D status. BMC Clin Pathol, 4, 11.
  32. Marcinkowska E (2001). A run for a membrane vitamin D receptor. Biol Signals Recept, 10, 341-9. https://doi.org/10.1159/000046902
  33. Matusiak D, Murillo G, Carroll RE, Mehta RG, a Benya RV (2005). Expression of vitamin D receptor and 25-hydroxyvitaminD3-1a-hydroxylase in normal and malignant human colon. Cancer Epidemiol Biomarkers Prev, 14, 2370-6. https://doi.org/10.1158/1055-9965.EPI-05-0257
  34. Minamitani K, Takahashi Y, Mingawa M, Yasuda T, Niimi H (1998). Difference in height associated with a translation start site polymorphism in the vitamin D receptor gene. Pediatr Res, 44, 628-32. https://doi.org/10.1203/00006450-199811000-00002
  35. Natrah MS, Ezat S, Syed MA, Rizal AM, Saperi S (2014). Quality of life in Malaysian colorectal cancer patients: a preliminary result. Asian Pac J Cancer Prev, 13, 957-62. https://doi.org/10.7314/APJCP.2012.13.3.957
  36. Onen IH, Ekmekci A, Eroglu M, et al (2008). Association of genetic polymorphism in vitamin D receptor gene and susceptibility to sporadic prostate cancer. Exp Biol Med (Maywood), 233, 1608-14. https://doi.org/10.3181/0803-RM-110
  37. Pereira F, Larriba MJ, Munoz A (2012). Vitamin D and colon cancer. Endocr relat cancer, 19, 51-71 https://doi.org/10.1530/ERC-11-0388
  38. Rasool S, Kadla SA, Khan T, et al (2013). Association of a VDR gene polymorphism with risk of colorectal cancer in Kashmir. Asian Pac J Cancer Prev, 14, 5833-7 https://doi.org/10.7314/APJCP.2013.14.10.5833
  39. Raimondi S, Johansson H, Maisonneuve P, Gandini S (2009). Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis, 30, 1170-80 https://doi.org/10.1093/carcin/bgp103
  40. Richetta AG, Silvestri V, Giancristoforo S, et al (2014). A-1012G promoter polymorphism of vitamin D receptor gene is associated with psoriasis risk and lower allele-specific expression. DNA Cell Biol, 33, 102-9. https://doi.org/10.1089/dna.2013.2217
  41. Ross AC, Taylor CL, Yaktine AL, Del valle HB (2011). Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press.
  42. Slattery ML (2007).Vitamin D receptor gene (VDR) associations with cancer. Nutr Rev, 65, 102-4. https://doi.org/10.1301/nr.2007.aug.S102-S104
  43. Slattery ML, Yakumo K, Hoffman M, Neuhausen S (2001). Variants of the VDR gene and risk of colon cancer (United States). Cancer Causes Control, 12, 359-64. https://doi.org/10.1023/A:1011280518278
  44. Seifert M, Tilgen W, Reichrath J (2009). Expression of 25-hydroxyvitamin D-1alpha-hydroxylase (1alphaOHase, CYP27B1) splice variants in HaCaT keratinocytes and other skin cells: modulation by culture conditions and UV-B treatment in vitro. Anticancer Res, 29, 3659-67.
  45. Thacher TD, Clarke BL (2010).Vitamin D insufficiency. Mayo Clin Proc, 86, 50-60.
  46. Tsiaras WG, Weinstock MA (2011). Factors influencing vitamin D status. Acta Derm Venereol, 91, 115-24.
  47. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C (2010).Vitamin D: a pleiotropic hormone. Kidney Int, 78, 140-5. https://doi.org/10.1038/ki.2010.17
  48. Vuolo L, Di Somma C, Faggiano A, Colao A (2012). Vitamin D and cancer. Front Endocrinol, 3, 58.
  49. Welsh J (2012). Cellular and molecular effects of vitamin D on carcinogenesis. Arch Biochem Biophys, 523, 107-14. https://doi.org/10.1016/j.abb.2011.10.019
  50. Woolcott CG, Wilkens LR, Nomura AM, et al (2010). Plasma 25-hydroxyvitamin D levels and the risk of colorectal cancer: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev, 19, 130-4. https://doi.org/10.1158/1055-9965.EPI-09-0475
  51. Yaylim-Eraltan I, Arzu Ergen H, Arikan S, et al (2007). Investigation of the VDR gene polymorphisms association with susceptibility to colorectal cancer. Cell Biochem Funct, 25,731-7. https://doi.org/10.1002/cbf.1386
  52. Yu K, Yang J, Jiang Y, Song R, Lu Q. (2014). Vitamin D receptor BsmI polymorphism and colorectal cancer risk: an updated analysis. Asian Pac J Cancer Prev, 15, 4801-7. https://doi.org/10.7314/APJCP.2014.15.12.4801
  53. Zheng W, Wong KE, Zhang Z, et al (2012). Inactivation of the vitamin D receptor in APCmin/1 mice reveals a critical role for the vitamin D receptor in intestinal tumor growth. Int J Cancer, 130, 10-9. https://doi.org/10.1002/ijc.25992
  54. Zinser GM, Mceleney K, Welsh J (2003). Characterization of mammary tumor cell lines from wild type and vitamin D3 receptor knockout mice. Mol Cell Endocrinol, 200, 1-2. https://doi.org/10.1016/S0303-7207(02)00408-2

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