Original Research


DOI :10.26650/experimed.2020.0002   IUP :10.26650/experimed.2020.0002    Full Text (PDF)

Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer

Murat ÖzdemirMehmet Tolgahan HakanDilara SönmezAli Kafadarİlhan YaylımÖzlem Küçükhüseyin

Recent studies imply the effects of micronutrient intake on the development of several cancers including primary brain cancer (PBC). The biological effects of vitamin D, a member of the fat-soluble vitamin family acting as a steroid hormone, was carried out by binding its receptor (VDR) through vitamin D-binding-protein (VDBP). The present study aims to investigate the effects of vitamin D levels and VDR rs2228570, VDR rs731236, VDBP 7041 polymorphisms on PBC development. The study group consisted of 71 patients and 84 controls. Vitamin D levels were determined by high-pressure liquid chromatography where polymorphisms by polymerase-chain-reaction and restriction fragment length polymorphism methods. The distribution of VDR rs2228570 variants in PBC and its subgroups were determined as FF>Ff>ff; VDBP rs7041 variants were TG> GG>TT, however, VDR rs731236 variants were Tt>TT>tt in PBC and meningioma and TT>Tt>tt in glioma. Vitamin D levels were measured below normal levels in all patients and control groups, which shows the deficiency in Turkish society in line with the literature. Our results show that low serum vitamin D level may be an individual risk factor in the development of brain tumors, however, VDR rs2228570 and rs731236 and VDBP rs7041 polymorphisms have no effect on the risk of disease development. 

DOI :10.26650/experimed.2020.0002   IUP :10.26650/experimed.2020.0002    Full Text (PDF)

D Vitamini Serum Düzeyleri ile D Vitamini Metabolizmasındaki Kritik Genlere Ait Varyasyonların Beyin Kanserinde İncelenmesi

Murat ÖzdemirMehmet Tolgahan HakanDilara SönmezAli Kafadarİlhan YaylımÖzlem Küçükhüseyin

Son çalışmalar, mikrobesin alımının primer beyin kanseri (PBC) dahil olmak üzere çeşitli kanser türlerinin gelişimi üzerindeki etkilerine işaret etmektedir. Yağda çözünen vitaminler sınıfında yer alan ve steroid hormon olarak etki gösteren D vitamini biyolojik etkilerini reseptörü (VDR) ile vitamin D bağlayıcı protein (VDBP) aracılığıyla gerçeklestirmektedir. Çalışmamızda, D vitamini düzeyleri ile VDR rs2228570, VDR rs731236, VDBP 7041 polimorfizmlerinin PBC gelişimi üzerindeki etkilerinin araştırılması amaçlanmıştır. Çalışma grubu, beyin kanseri tanısı konmuş 71 hasta ile 84 sağlıklı bireyden oluşturulmuştur. D vitamini düzeyi, yüksek basınçlı sıvı kromatografisi yöntemiyle, VDR FokI (rs2228570), TaqI (rs731236) ve VDBP rs7041 polimorfizmleri polimeraz zincir reaksiyonu ve restriksiyon parça uzunluk polimorfizmi yöntemleriyle belirlenmiştir. Çalışmamızda VDR FokI gen varyantlarına ait dağılım primer beyin kanseri ve alt gruplarında FF>Ff>ff; VDBP rs7041 varyantları TG>GG>TT olarak, VDR TaqI varyantlarının ise primer beyin kanseri ve meningiomada Tt>TT>tt, gliomada TT>Tt>tt olduğu tespit edilmiştir. D Vitamini düzeyleri tüm hasta gruplarında ve kontrol grubunda normal düzeyinin altında ölçülmüş, bu durum Türk toplumundaki vitamin D düzeylerinin literatürle uyumlu bir şekilde düşük seviyede olduğunu göstermiştir. Çalışmamız sonuçları, beyin tümörleri gelişiminde düşük serum D vitamini seviyesinin bireysel bir risk faktörü olabileceğini, ancak VDR rs2228570 ile rs731236 ve VDBP rs7041 polimorfizmlerinin hastalık gelişim riskine etkisinin olmadığını göstermektedir


PDF View

References

  • 1. Araştırma UK. Dünyadaki Beyin Kanseri Vakası ve ölüm İstatistiği 2012 [updated 27.04.2018. Available from: http://globocan.iarc.fr/ Pages/fact_sheets_population.aspx?country=900. google scholar
  • 2. Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS, et al. Genome-wide association study of glioma and meta-analysis. Human Genetics 2012; 131(12): 1877-88. [CrossRef] google scholar
  • 3. Toptaş B, Kafadar AM, Cacina C, Turan S, Yurdum LM, Yiğitbaşı N, et al. The vitamin D receptor (VDR) gene polymorphisms in Turkish brain cancer patients. BioMed Research International 2013; 2013. [CrossRef] google scholar
  • 4. Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ. Vitamin D: metabolism. Endocrinology and Metabolism Clinics 2010; 39(2): 243-53. [CrossRef] google scholar
  • 5. Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Reviews Cancer 2007; 7(9): 684. [CrossRef] google scholar
  • 6. Cornet A, Baudet C, Neveu I, Baron‐Van Evercooren A, Brachet P, Naveilhan P. 1, 25‐dihydroxyvitamin D3 regulates the expression of VDR and NGF gene in Schwann cells in vitro. Journal of Neuroscience Research 1998; 53(6): 742-6. [CrossRef] google scholar
  • 7. Gomme PT, Bertolini J. Therapeutic potential of vitamin D-binding protein. Trends in Biotechnology 2004; 22(7): 340-5. [CrossRef] google scholar
  • 8. Burkert R, McGrath J, Eyles D. Vitamin D receptor expression in the embryonic rat brain. Neuroscience Research Communications 2003; 33(1): 63-71. [CrossRef] google scholar
  • 9. Baas D, Prüfer K, Ittel ME, Kuchler‐Bopp S, Labourdette G, Sarliève LL, et al. Rat oligodendrocytes express the vitamin D3 receptor and respond to 1, 25‐dihydroxyvitamin D3. Glia 2000; 31(1): 5968. [CrossRef] google scholar
  • 10. Boontanrart M, Hall SD, Spanier JA, Hayes CE, Olson JK. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism. Journal of Neuroimmunology 2016; 292: 126-36. [CrossRef] google scholar
  • 11. Naveilhan P, Neveu I, Baudet C, Ohyama K, Brachet P, Wion D. Expression of 25 (OH) vitamin D3 24-hydroxylase gene in glial cells. Neuroreport 1993; 5(3): 255-7. [CrossRef] google scholar
  • 12. Delanghe JR, Speeckaert R, Speeckaert MM. Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best Practice & Research Clinical Endocrinology & Metabolism 2015; 29(5): 773-86. [CrossRef] google scholar
  • 13. Sweeney C, Curtin K, Murtaugh MA, Caan BJ, Potter JD, Slattery ML. Haplotype analysis of common vitamin D receptor variants and colon and rectal cancers. Cancer Epidemiology and Prevention Biomarkers 2006; 15(4): 744-9. [CrossRef] google scholar
  • 14. Köstner K, Denzer N, Mueller CS, Klein R, Tilgen W, Reichrath J. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Research 2009; 29(9): 3511-36. google scholar
  • 15. Zhou L, Zhang X, Chen X, Liu L, Lu C, Tang X, et al. GC Glu416Asp and Thr420Lys polymorphisms contribute to gastrointestinal cancer susceptibility in a Chinese population. International Journal of Clinical and Experimental Medicine 2012; 5(1): 72. google scholar
  • 16. Atoum MF, Tchoporyan MN. Association between circulating vitamin D, the Taq1 vitamin D receptor gene polymorphism and colorectal cancer risk among Jordanians. Asian Pac J Cancer Prev 2014; 15(17): 7337-41. [CrossRef] google scholar
  • 17. Miyazaki T, Ishikawa E, Matsuda M, Akutsu H, Osuka S, Sakamoto N, et al. Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome. Journal of Neuro-Oncology 2017; 133(2): 277-85. [CrossRef] google scholar
  • 18. Bakanlığı TS. Kanser İstatistikleri 2017 [updated 27.04.2018. Available from: http://kanser.gov.tr/Dosya/2017Haberler/2017_4_subat.pdf. google scholar
  • 19. Mohr SB. A brief history of vitamin D and cancer prevention. Annals of Epidemiology 2009; 19(2): 79-83. [CrossRef] 20. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Annals of Epidemiology 2009; 19(2): 73-8. [CrossRef] google scholar
  • 21. Öğüş E, Sürer H, Kılınç A, Fidancı V, Yılmaz G, Dindar N, et al. D Vitamini düzeylerinin aylara, cinsiyete ve yaşa göre değerlendirilmesi. Ankara Medical Journal 2014; 15(1). [CrossRef] google scholar
  • 22. Grant WB. A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D. Dermato-Endocrinology 2009; 1(1): 25-33. [CrossRef] google scholar
  • 23. Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, et al. Plasma 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiology and Prevention Biomarkers 2005; 14(8): 1991-7. [CrossRef] google scholar
  • 24. Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, et al. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. European Journal of Cancer 2005; 41(8): 1164-9. [CrossRef] google scholar
  • 25. Tworoger SS, Lee I-M, Buring JE, Rosner B, Hollis BW, Hankinson SE. Plasma 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiology and Prevention Biomarkers 2007; 16(4): 783-8. [CrossRef] google scholar
  • 26. Garland CF, Mohr SB, Gorham ED, Grant WB, Garland FC. Role of ultraviolet B irradiance and vitamin D in prevention of ovarian cancer. American Journal of Preventive Medicine 2006; 31(6): 512-4. [CrossRef] google scholar
  • 27. Shi L, Nechuta S, Gao Y-T, Zheng Y, Dorjgochoo T, Wu J, et al. Correlates of 25-hydroxyvitamin D among Chinese breast cancer patients. PLoS One 2014; 9(1): e86467. [CrossRef] google scholar
  • 28. Mezawa H, Sugiura T, Watanabe M, Norizoe C, Takahashi D, Shimojima A, et al. Serum vitamin D levels and survival of patients with colorectal cancer: post-hoc analysis of a prospective cohort study. BMC Cancer 2010; 10(1): 347. [CrossRef] google scholar
  • 29. Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative metaanalysis. American Journal of Preventive Medicine 2007; 32(3): 210-6. [CrossRef] google scholar
  • 30. Gromowski T, Gapska P, Scott RJ, Kąklewski K, Marciniak W, Durda K, et al. Serum 25 (OH) D concentration, common variants of the VDR gene and lung cancer occurrence. International Journal of Cancer 2017; 141(2): 336-41. [CrossRef] google scholar
  • 31. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends in Endocrinology & Metabolism 2002; 13(3): 100-5. [CrossRef] google scholar
  • 32. Bhanushali AA, Lajpal N, Kulkarni SS, Chavan SS, Bagadi SS, Das BR. Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels. Indian Journal of Human Genetics 2009; 15(3): 108. [CrossRef] google scholar
  • 33. Cplston K, Colston MJ, Feldman D. 1, 25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology 1981; 108(3): 1083-6. [CrossRef] google scholar
  • 34. Naveilhan P, Berger F, Haddad K, Barbot N, Benabid AL, Brachet P, et al. Induction of glioma cell death by 1, 25 (OH) 2 vitamin D3: towards an endocrine therapy of brain tumors? Journal of Neuroscience Research 1994; 37(2): 271-7. [CrossRef] google scholar
  • 35. Baudet C, Chevalier G, Naveilhan P, Binderup L, Brachet P, Wion D. Cytotoxic effects of 1α, 25-dihydroxyvitamin D3 and synthetic vitamin D3 analogues on a glioma cell line. Cancer Letters 1996; 100(1-2): 3-10. [CrossRef] google scholar
  • 36. Trouillas P, Honnorat J, Bret P, Jouvet A, Gerard J-P. Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alpha-hydroxycholecalciferol. Journal of Neuro-oncology 2001; 51(1): 57-66. [CrossRef] google scholar
  • 37. Moossavi M, Parsamanesh N, Mohammadoo‐Khorasani M, Moosavi M, Tavakkoli T, Fakharian T, et al. Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South‐Khorasan of Iran. Journal of Cellular Biochemistry 2018; 119(10): 8190-4. [CrossRef] google scholar
  • 38. Yilmaz B, Tokuc GA, Koc A, Yesil E. Investigation of vitamin D recep tor gene polymorphism in pediatric patients with brain cancer. Indian journal of medical and paediatric oncology: official journal of Indian Society of Medical & Paediatric Oncology 2017; 38(2): 128. google scholar
  • 39. Tang C, Chen N, Wu M, Yuan H, Du Y. Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Research and Treatment 2009; 117(2): 391. [CrossRef] google scholar
  • 40. Chen L, Wei J, Zhang S, Lou Z, Wang X, Ren Y, et al. Association of VDR gene TaqI polymorphism with the susceptibility to prostate cancer in Asian population evaluated by an updated systematic meta-analysis. Onco Targets and Therapy. 2018; 11: 3267. [CrossRef] google scholar
  • 41. Baykara O, Erşen E, Batur Ş, Buyru N. Role of vitamin D binding protein (VDBP) gene polymorphisms in lung cancer. Turkish Journal of Thoracic and Cardiovascular Surgery 2017; 25(4). [CrossRef] google scholar
  • 42. Anderson LN, Cotterchio M, Cole DE, Knight JA. Vitamin D-related genetic variants, interactions with vitamin D exposure, and breast cancer risk among Caucasian women in Ontario. Cancer Epidemiology and Prevention Biomarkers 2011; 20(8): 1708-17. [CrossRef] google scholar
  • 43. Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes & Control 2005; 16(2): 83-95. [CrossRef] google scholar
  • 44. Jeon S-M, Shin E-A. Exploring vitamin D metabolism and function in cancer. Experimental & Molecular Medicine 2018; 50(4): 20. [CrossRef] google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Özdemir, M., Hakan, M., Sönmez, D., Kafadar, A., Yaylım, İ., & Küçükhüseyin, Ö. (2020). Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer. Experimed, 10(1), 16-24. https://doi.org/10.26650/experimed.2020.0002


AMA

Özdemir M, Hakan M, Sönmez D, Kafadar A, Yaylım İ, Küçükhüseyin Ö. Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer. Experimed. 2020;10(1):16-24. https://doi.org/10.26650/experimed.2020.0002


ABNT

Özdemir, M.; Hakan, M.; Sönmez, D.; Kafadar, A.; Yaylım, İ.; Küçükhüseyin, Ö. Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer. Experimed, [Publisher Location], v. 10, n. 1, p. 16-24, 2020.


Chicago: Author-Date Style

Özdemir, Murat, and Mehmet Tolgahan Hakan and Dilara Sönmez and Ali Kafadar and İlhan Yaylım and Özlem Küçükhüseyin. 2020. “Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer.” Experimed 10, no. 1: 16-24. https://doi.org/10.26650/experimed.2020.0002


Chicago: Humanities Style

Özdemir, Murat, and Mehmet Tolgahan Hakan and Dilara Sönmez and Ali Kafadar and İlhan Yaylım and Özlem Küçükhüseyin. Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer.” Experimed 10, no. 1 (May. 2024): 16-24. https://doi.org/10.26650/experimed.2020.0002


Harvard: Australian Style

Özdemir, M & Hakan, M & Sönmez, D & Kafadar, A & Yaylım, İ & Küçükhüseyin, Ö 2020, 'Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer', Experimed, vol. 10, no. 1, pp. 16-24, viewed 11 May. 2024, https://doi.org/10.26650/experimed.2020.0002


Harvard: Author-Date Style

Özdemir, M. and Hakan, M. and Sönmez, D. and Kafadar, A. and Yaylım, İ. and Küçükhüseyin, Ö. (2020) ‘Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer’, Experimed, 10(1), pp. 16-24. https://doi.org/10.26650/experimed.2020.0002 (11 May. 2024).


MLA

Özdemir, Murat, and Mehmet Tolgahan Hakan and Dilara Sönmez and Ali Kafadar and İlhan Yaylım and Özlem Küçükhüseyin. Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer.” Experimed, vol. 10, no. 1, 2020, pp. 16-24. [Database Container], https://doi.org/10.26650/experimed.2020.0002


Vancouver

Özdemir M, Hakan M, Sönmez D, Kafadar A, Yaylım İ, Küçükhüseyin Ö. Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer. Experimed [Internet]. 11 May. 2024 [cited 11 May. 2024];10(1):16-24. Available from: https://doi.org/10.26650/experimed.2020.0002 doi: 10.26650/experimed.2020.0002


ISNAD

Özdemir, Murat - Hakan, Mehmet Tolgahan - Sönmez, Dilara - Kafadar, Ali - Yaylım, İlhan - Küçükhüseyin, Özlem. Investigation of Critical Genetic Variations of Vitamin D Metabolism and Vitamin D Serum Levels in Brain Cancer”. Experimed 10/1 (May. 2024): 16-24. https://doi.org/10.26650/experimed.2020.0002



TIMELINE


Submitted18.02.2020
Accepted16.03.2020
Published Online13.04.2020

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.