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The Fok1 Vitamin D Receptor Gene Polymorphism and 25(OH) D Serum Levels and Prostate Cancer among Jordanian Men

  • Published : 2015.04.03

Abstract

Background: Prostate cancer (PCa) is one of the most commonly diagnosed neoplasms and the second leading cause of cancer death in men in the Western world. Vitamin D (1,25dihydroxy vitamin D) is linked to many biological processes that influence oncogenesis but data on relations between its genetic variants and cancer risk have been inconsistent. The aim of this study was to determine associations between a vitamin D genetic polymorphism and 25-hydroxyvitamin D [25(OH)D] levels and prostate cancer. Materials and Methods: Genomic DNA was extracted from 124 Jordanian prostate cancer patients and 100 healthy volunteers. Ethical approval was granted from the ethical committee at Hashemite University and written consent was given by all patients. PCR was used to amplify the vitamin D receptor Fok1 polymorphism fragment. 25(OH)D serum levels were measured by competitive immunoassay. Results: All genotypes were in Hardy-Weinberg equilibrium. Genotype frequency for Fok1 genotypes FF, Ff and ff was 30.7%, 61.3% and 8.06%, for prostate cancer patients, while frequencies for the control group was 28.0%, 66.0% and 6.0%, respectively, with no significant differences. Vitamin D serum level was significantly lower in prostate cancer patients (mean 7.7 ng/ml) compared to the control group (21.8 ng/ml). No significant association was noted between 25(OH)D and VDR Fok1 gene polymorphism among Jordanians overall, but significant associations were evident among prostate cancer patients (FF, Ff and ff : 25(OH)D levels of 6.2, 8.2 and 9.9) and controls (19.0, 22.5 and 26.3, respectively). An inverse association was noted between 25(OH)D serum level less than 10ng/ml and prostate cancer risk (OR 35.5 and 95% CI 14.3- 88.0). Conclusions: There is strong inverse association between 25(OH)D serum level less than 10ng/ml level and prostate cancer risk.

Keywords

References

  1. Atoum M, Tchoporyan MN (2014). Association between circulatory vitamin D, Taq1 vitamin D receptor gene polymorphism and colorectal cancer risk among Jordanians. Asian Pac J Cancer Prev, 15, 7337-41. https://doi.org/10.7314/APJCP.2014.15.17.7337
  2. Baker, AR, McDonnell DP, Hughes M, et al (1988). Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA, 85, 3294-8. https://doi.org/10.1073/pnas.85.10.3294
  3. Brown, AJ, Dusso A, Slatopolsky E (1999). Vitamin D. Am J Physiol, 277, 157-75.
  4. Crofts La, Hancock MS, Morrison NA, Eisman JA (1998). Multiple promoters direct the tissue-specific expression of novel n-terminal variant human vitamin d receptor gene transcripts. Proc Natl Acad Sci USA, 95, 10529-34. https://doi.org/10.1073/pnas.95.18.10529
  5. Donkena KV, Young C (2011). Vitamin D, sunlight and prostate cancer risk. Adv Prev Med, 281863, 13.
  6. Grant WB. Vitamin D status: ready for guiding prostate cancer diagnosis and treatment. Clin Cancer Res, 20, 2241-3.
  7. Gross, C, Stamey T, Hancock S and Feldman D (1998). Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol). J Urol, 159, 2035-9; 2039-40. https://doi.org/10.1016/S0022-5347(01)63236-1
  8. Guo Z, Wen J, Kan Q, et al (2013). Lack of association between vitamin D receptor gene FokI and BsmI polymorphisms and prostate cancer risk: an updated meta-analysis involving 21,756 subjects. Tumour Biol, 34, 3189-3200. https://doi.org/10.1007/s13277-013-0889-6
  9. Habuchi T, Suzuki T, Sasaki R, et al (2000). Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population. Cancer Res, 60, 305-8.
  10. Haussler MR, Whitfield GK, Haussler CA, et al (1998). The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res, 13, 325-49. https://doi.org/10.1359/jbmr.1998.13.3.325
  11. Huang SP, Huang CY, Wu WJ, et al (2006). Association of Vitamin D receptor Fok1 polymorphism with prostate cancer risk, Clinico-pathological features and recurrence of prostate specific antigen after radical prostatectomy. Int J Cancer, 119, 1902-7. https://doi.org/10.1002/ijc.22053
  12. Hayes VM, Severi G, Padilla EJ, et al (2005). Genetic variants in the vitamin D receptor gene and prostate cancer risk. Cancer Epidemiol Biomarkers Prev, 14, 997-9. https://doi.org/10.1158/1055-9965.EPI-04-0660
  13. Holt SK, Kwon EM, Peters U, Ostrander EA, Stanford JL (2009). Vitamin D pathway gene variants and prostate cancer risk. Cancer Epidemiol Biomarkers Prev, 18, 1929-33. https://doi.org/10.1158/1055-9965.EPI-09-0113
  14. Holund B (1980). Latent prostatic cancer in a consecutive autopsy series. Scand J Urol Nephrol, 14, 29-35. https://doi.org/10.3109/00365598009181186
  15. Hughes, MR, Malloy PJ, Kieback DG, et al (1988). point mutations in the human vitamin d receptor gene associated with hypocalcemic rickets. Science 242, 1702-5. https://doi.org/10.1126/science.2849209
  16. Ingles, SA, Coetzee GA, Ross RK, et al (1998). Association of prostate cancer with vitamin D receptor haplotypes in African-Americans. Cancer Res, 58, 1620-3.
  17. Jemal A, Siegel R, Ward E, et al (2006) CA Cancer J Clin, 56, 106-30. https://doi.org/10.3322/canjclin.56.2.106
  18. Li H, Stampfer MJ, Hollis JB, et al (2007). A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med, 4, 103. https://doi.org/10.1371/journal.pmed.0040103
  19. Li XY, Boudjelal M, Xiao JH, et al (1999). 1,25-Dihydroxyvitamin D3 increases nuclear Vitamin D3 receptors by blocking ubiquitin/proteasome-mediated degradation in human skin." Mol Endocrinol 13, 1686-94. https://doi.org/10.1210/mend.13.10.0362
  20. Lichtenstein P, Holm NV, Verkasalo PK, et al (2000). Skytthe A and Hemminki K. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med, 343, 78-85. https://doi.org/10.1056/NEJM200007133430201
  21. Luong, KV and Nguyen LT (2010). The beneficial role of vitamin d and its analogs in cancer treatment and prevention. Crit Rev Oncol Hematol, 73, 192-201. https://doi.org/10.1016/j.critrevonc.2009.04.008
  22. Miller GJ, Stapleton GE, Ferrara JA, et al (1992). The human prostatic carcinoma cell line lncap expresses biologically active, specific receptors for 1 alpha,25-dihydroxyvitamin D3. Cancer Res, 52, 515-20.
  23. Nair RI, Maseeh A (2012). Vitamin D the sun shine vitamin. J Pharmacol Pharmacother. 3, 118-126.
  24. Nwosu V, Carpten J, Trent JM, Sheridan R (2001). Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. Hum Mol Genet, 10, 2313-8. https://doi.org/10.1093/hmg/10.20.2313
  25. Oakley-Girvan I, Feldman D, Eccleshall TR, et al (2004). Risk of Early-onset prostate cancer in relation to germ line polymorphisms of the vitamin D receptor. Cancer Epidemiol Biomarkers Prev, 13, 1325-30.
  26. Parkin, DM, Bray FI, Devesa SS (2001). Cancer burden in the Year 2000. The global picture. Eur J Cancer, 37, 4-66.
  27. Peehl DM, Skowronski RJ, Leung GK, (1994). Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res, 54, 805-10.
  28. Polek, TC, Weigel NL. Vitamin D and prostate cancer (2002). J Androl, 23, 9-17.
  29. Saijo T, It M, Takeda E, et al (1991). A unique mutation in the vitamin d receptor gene in three japanese patients with vitamin d-dependent rickets type ii: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet, 49, 668-73.
  30. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013 CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  31. Tzonou A, Signorello LB, Lagiou P, et al (1999). Diet and cancer of the prostate: a case-control study in Greece. Int J Cancer, 80, 704-8. https://doi.org/10.1002/(SICI)1097-0215(19990301)80:5<704::AID-IJC13>3.0.CO;2-Z
  32. Wu-Wong JR (2007). Vitamin D receptor: a highly versatile nuclear receptor. Kidney Int, 72, 237-9. https://doi.org/10.1038/sj.ki.5002428
  33. Xu J, Zheng SL, Komiya A, et al (2003). Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Am J Hum Genet, 72, 208-12. https://doi.org/10.1086/345802
  34. Yin, M, Wei S and Wei Q (2009). Vitamin D receptor genetic polymorphisms and prostate cancer risk: A meta-analysis of 36 published studies. Int J Clin Exp Med, 2, 159-75.
  35. Yousaf N, Afzal S, Hayat T,et al (2014). Association of vitamin D receptor gene polymorphism with prostate cancer risk in Pakistani population. Asian Pac J Cancer Prev, 15, 10009-13. https://doi.org/10.7314/APJCP.2014.15.22.10009
  36. Yu, S. and Cantorna MT (2011). Epigenetic reduction in invariant nkt cells following in utero vitamin d deficiency in mice. J Immunol, 186, 1384-90. https://doi.org/10.4049/jimmunol.1002545
  37. Zhang X, Ho SM (2011). Epigenetics meets endocrinology. J Mol Endocrinol, 46, 11-32. https://doi.org/10.1677/JME-10-0053
  38. Zhang Q, Shan Y (2013). Genetic polymorphism of vitamin D receptor and risk of prostate cancer: a meta -analysis. J Boun, 18, 961-9.

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