Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Association of Vitamin D Receptor Gene Polymorphisms with Prostate Cancer Risk in the Pakistani Population

  • Yousaf, Nageen (Khyber Girls Medical Colleg) ;
  • Afzal, Sibtain (Prince Naif Center for Immunology Research, College of Medicine, King Saud University) ;
  • Hayat, Tehreem (Department of Biotechnology, COMSATS Institute of Information Technology) ;
  • Shah, Jasmin (Institute of Chemical Sciences, Peshawar University) ;
  • Ahmad, Nafees (Department of Biomedical and Genetic Engineering) ;
  • Abbasi, Rashda (Department of Biomedical and Genetic Engineering) ;
  • Ramzan, Khushnooda (Department of Genetics, King Faisal Specialist Hospital and Research Centre) ;
  • Jan, Rasul (University Peshawar) ;
  • Khan, Imran (Institute of Basic Medical Sciences, Khyber Medical University) ;
  • Ahmed, Jawad (Institute of Basic Medical Sciences, Khyber Medical University) ;
  • Siraj, Sami (Institute of Basic Medical Sciences, Khyber Medical University)
  • Published : 2014.12.18
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Vitamin D receptor (VDR) gene has been a subject of extensive pharmacogenetic research recently. Association studies between different types of cancers including prostate cancer (PCa) and VDR gene polymorphism have also been conducted. The objective of this study was to find possible associations between PCa and VDR gene polymorphisms in the Pakistani population. Materials and Methods: A total of 162 subjects, including prostate cancer patients and controls, were genotyped for Apa I, Taq I and Fok I polymorphisms in the VDR gene using allele specific PCR, PCR-RFLP and direct DNA sequencing. Allelic frequencies were tested for Hardy-Weinberg equilibrium and associations between the genetic markers and PCa were calculated using logistic regression. Results: Apa I CC genotype was found to have strongest association with PCa risk, and "A" genotype was found to have protective effect. Fok I and Taq I did not have appreciable levels of association with PCa, although Taq I "TC" heterozygotes seemed to have some protective effect. Similarly the "C" allele of Fok I also seemed to have protective effect. Conclusions: To our knowledge, this is the first report showing association between VDR gene polymorphisms and PCa in Pakistan. Our findings may be somewhat skewed because of small sample size and tendency of consanguineous marriages in Pakistani society; nevertheless, it shows the trend of association and protective effects of certain VDR gene polymorphisms against PCa.

Keywords

References

  1. Arshad H, Ahmad Z (2013). Overview of benign and malignant prostatic disease in Pakistani patients: a clinical and histopathological perspective. Asian Pac J Cancer Prev, 14, 3005-10. https://doi.org/10.7314/APJCP.2013.14.5.3005
  2. Bai Y, Yu Y, Yu B, et al (2009). Association of vitamin D receptor polymorphisms with the risk of prostate cancer in the Han population of Southern China. BMC Med Genet, 10, 125. https://doi.org/10.1186/1471-2350-10-125
  3. Beer TM, Myrthue A (2004). Calcitriol in cancer treatment: from the lab to the clinic. Mol Cancer Ther, 3, 373-81.
  4. Chen L, Davey Smith G, Evans DM, et al (2009). Genetic variants in the vitamin d receptor are associated with advanced prostate cancer at diagnosis: findings from the prostate testing for cancer and treatment study and a systematic review. Cancer Epidemiol Biomarkers Prev, 18, 2874-81. https://doi.org/10.1158/1055-9965.EPI-09-0544
  5. Dianat SS, Margreiter M, Eckersberger E, et al (2009). Gene polymorphisms and prostate cancer: the evidence. BJU Int, 104, 1560-72. https://doi.org/10.1111/j.1464-410X.2009.08973.x
  6. Feldman D, Skowronski RJ, Peehl DM (1995). Vitamin D and prostate cancer. Adv Exp Med Biol, 375, 53-63.
  7. Giovannucci E (2009). Vitamin D and cancer incidence in the Harvard cohorts. Ann Epidemiol, 19, 84-8. https://doi.org/10.1016/j.annepidem.2007.12.002
  8. Gross C, Krishnan AV, Malloy PJ, et al (1998). The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. J Bone Miner Res, 13, 1691-9. https://doi.org/10.1359/jbmr.1998.13.11.1691
  9. 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, 3189-200. https://doi.org/10.1007/s13277-013-0889-6
  10. Harnden P, Naylor B, Shelley MD, et al (2008). The clinical management of patients with a small volume of prostatic cancer on biopsy: what are the risks of progression? A systematic review and meta-analysis. Cancer, 112, 971-81. https://doi.org/10.1002/cncr.23277
  11. Haussler MR, Jurutka PW, Hsieh JC, et al (1995). New understanding of the molecular mechanism of receptormediated genomic actions of the vitamin D hormone. Bone, 17, 33-8. https://doi.org/10.1016/8756-3282(95)00205-R
  12. Hendrickson WK, Flavin R, Kasperzyk JL, et al (2011). Vitamin D receptor protein expression in tumor tissue and prostate cancer progression. J Clin Oncol, 29, 2378-85. https://doi.org/10.1200/JCO.2010.30.9880
  13. Jamal S, Atique M, Khadim MT (2014). Changing pattern of malignancies: analysis of histopathology based tumour registry data and comparison of three decades at armed forces institute of pathology, Rawalpindi, Pakistan. J Pak Med Assoc, 64, 24-7.
  14. Jensen SS, Madsen MW, Lukas J, et al (2001). Inhibitory effects of 1alpha,25-dihydroxyvitamin D(3) on the G(1)-S phasecontrolling machinery. Mol Endocrinol, 15, 1370-80.
  15. Koressaar T, Remm M (2007). Enhancements and modifications of primer design program Primer3. Bioinformatics, 23, 1289-91. https://doi.org/10.1093/bioinformatics/btm091
  16. Krishnan AV, Feldman D (2010). Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment. Endocr Relat Cancer, 17, 19-38.
  17. Krishnan AV, Peehl DM, Feldman D (2003). Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression. J Cell Biochem, 88, 363-71. https://doi.org/10.1002/jcb.10334
  18. Lou YR, Qiao S, Talonpoika R, et al (2004). The role of Vitamin D3 metabolism in prostate cancer. J Steroid Biochem Mol Biol, 92, 317-25. https://doi.org/10.1016/j.jsbmb.2004.10.007
  19. Medeiros R, Morais A, Vasconcelos A, et al (2002). The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population. J Hum Genet, 47, 413-8. https://doi.org/10.1007/s100380200060
  20. Miller GJ, Stapleton GE, Hedlund TE, et al (1995). Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res, 1, 997-1003.
  21. Mishra DK, Bid HK, Srivastava DS, et al (2005). Association of vitamin D receptor gene polymorphism and risk of prostate cancer in India. Urol Int, 74, 315-8. https://doi.org/10.1159/000084429
  22. Nelson WG, De Marzo AM, Isaacs WB (2003). Prostate cancer. N Engl J Med, 349, 366-81. https://doi.org/10.1056/NEJMra021562
  23. Oh JJ, Byun SS, Lee SE, et al (2014). Genetic variations in VDR associated with prostate cancer risk and progression in a Korean population. Gene, 533, 86-93. https://doi.org/10.1016/j.gene.2013.09.119
  24. Onen IH, Ekmekci A, Eroglu M, et al (2008). Association of genetic polymorphisms 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
  25. Peehl DM, Skowronski RJ, Leung GK, et al (1994). Antiproliferative effects of 1, 25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res, 54, 805-10.
  26. Raimondi S, Johansson H, Maisonneuve P, et al (2009). Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis, 30, 1170-80. https://doi.org/10.1093/carcin/bgp103
  27. Rodriguez S, Gaunt TR, Day IN (2009). Hardy-weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol, 169, 505-14.
  28. Scher HI, Heller G (2000). Clinical states in prostate cancer: toward a dynamic model of disease progression. Urology, 55, 323-7. https://doi.org/10.1016/S0090-4295(99)00471-9
  29. Sporn MB, Suh N (2002). Chemoprevention: an essential approach to controlling cancer. Nat Rev Cancer, 2, 537-43. https://doi.org/10.1038/nrc844
  30. Stangelberger A, Waldert M, Djavan B (2008). Prostate cancer in elderly men. Rev Urol, 10, 111-9.
  31. Sun T, Lee GS, Werner L, et al (2010). Inherited variations in AR, ESR1, and ESR2 genes are not associated with prostate cancer aggressiveness or with efficacy of androgen deprivation therapy. Cancer Epidemiol Biomarkers Prev, 19, 1871-8. https://doi.org/10.1158/1055-9965.EPI-10-0216
  32. Trump DL, Hershberger PA, Bernardi RJ, et al (2004). Antitumor activity of calcitriol: pre-clinical and clinical studies. J Steroid Biochem Mol Biol, 89-90, 519-26. https://doi.org/10.1016/j.jsbmb.2004.03.068
  33. Uitterlinden AG, Fang Y, Van Meurs JB, et al (2004). Genetics and biology of vitamin D receptor polymorphisms. Gene, 338, 143-56. https://doi.org/10.1016/j.gene.2004.05.014
  34. Untergasser A, Cutcutache I, Koressaar T, et al (2012). Primer3- new capabilities and interfaces. Nucleic Acids Res, 40, 115.
  35. Vanoirbeek E, Krishnan A, Eelen G, et al (2011). The anti-cancer and anti-inflammatory actions of 1, 25(OH)(2)D(3). Best Pract Res Clin Endocrinol Metab, 25, 593-604. https://doi.org/10.1016/j.beem.2011.05.001
  36. Wang X, Wang S, Lin YW, et al (2012). Angiotensin-converting enzyme insertion/deletion polymorphism and the risk of prostate cancer in the Han population of China. Med Oncol, 29, 1964-71. https://doi.org/10.1007/s12032-011-0051-5
  37. Whitfield GK, Remus LS, Jurutka PW, et al (2001). Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol, 177, 145-59. https://doi.org/10.1016/S0303-7207(01)00406-3
  38. Xu Y, He B, Pan Y, et al (2014). Systematic review and metaanalysis on vitamin D receptor polymorphisms and cancer risk. Tumour Biol, 35, 4153-69. https://doi.org/10.1007/s13277-013-1544-y
  39. Yin M, Wei S, 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.
  40. Zhang Q, Shan Y (2013). Genetic polymorphisms of vitamin D receptor and the risk of prostate cancer: a meta-analysis. J BUON, 18, 961-9.

Cited by

  1. The Fok1 Vitamin D Receptor Gene Polymorphism and 25(OH) D Serum Levels and Prostate Cancer among Jordanian Men vol.16, pp.6, 2015, https://doi.org/10.7314/APJCP.2015.16.6.2227
  2. Role of vitamin D receptor gene Cdx2 and Apa1 polymorphisms in prostate cancer susceptibility: a meta-analysis vol.16, pp.1, 2016, https://doi.org/10.1186/s12885-016-2722-2
  3. gene polymorphism with sex- and non-sex-associated cancers: A meta-analysis vol.39, pp.10, 2017, https://doi.org/10.1177/1010428317727164
  4. I) with prostate cancer: a new meta-analysis vol.45, pp.1, 2017, https://doi.org/10.1177/0300060516668939