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

Yıl 2020, , 16 - 24, 13.03.2020

Murat Özdemir M. Tolgahan Hakan Dilara Sönmez Ali Kafadar İlhan Yaylım Özlem Küçükhüseyin

https://doi.org/10.26650/experimed.2020.0002

Öz

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.

Anahtar Kelimeler

Brain tumors, glioma, meningioma, VDR, VDBP, vitamin D

Destekleyen Kurum

The present study was supported by a grant from the Scientific Research Projects Coordination Unit of Istanbul University (Project No: TYL-2018-28203).

Proje Numarası

Project No: TYL-2018-28203

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

Öz

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.

Anahtar Kelimeler

Beyin tümörleri, glioma, meningioma, VDR, VDBP, D vitamini

Proje Numarası

Project No: TYL-2018-28203

Kaynakça

• 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.
• 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]
• 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]
• 4. Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ. Vitamin D: metabolism. Endocrinology and Metabolism Clinics 2010; 39(2): 243-53. [CrossRef]
• 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]
• 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]
• 7. Gomme PT, Bertolini J. Therapeutic potential of vitamin D-binding protein. Trends in Biotechnology 2004; 22(7): 340-5. [CrossRef]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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.
• 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.
• 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]
• 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]
• 18. Bakanlığı TS. Kanser İstatistikleri 2017 [updated 27.04.2018. Available from: http://kanser.gov.tr/Dosya/2017Haberler/2017_4_subat.pdf.
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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.
• 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]
• 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]
• 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]
• 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]
• 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]
• 44. Jeon S-M, Shin E-A. Exploring vitamin D metabolism and function in cancer. Experimental & Molecular Medicine 2018; 50(4): 20. [CrossRef]