Evaluation of the Relationship between MTHFR C677T Single Nucleotide Polymorphism and Prostate Cancer in Hatay

Yıl 2014, Cilt: 5 Sayı: 19, 29 - 36, 03.03.2015

Müzeyyen İzmirli Hasret Ecevit Bülent Göğebakan Mehmet İnci Davut Alptekin

https://doi.org/10.17944/mkutfd.54258

Öz

MTHFR (Methylenetatrahydrofolate reductase) is one of the most important enzymes because of its function about folate metabolism and DNA synthesis pathways. The C677T single
nucleotide polymorphism in the gene encoding the enzyme, have been associated with many diseases including prostate cancer. We aimed to evaluate the association between the polymorphism and prostate cancer by comparing the results between patients and controls. Patients, who suffer from prostate cancer (n: 20) and healthy controls (n: 20) were included the study. First of all, DNA isolation was performed from the blood samples that are taken in hemogram tubes. After reproducing the region about relevant polymorphism by Polymerase Chain Reaction (PCR), it was cut by Restriction Fragment Length Polymorphism (RFLP) with suitable enzyme and viewed by Polyacrylamide gel electrophoresis (PAGE). When the results evaluated MTHFR C677T polymorphisms genotypes, the ratios were CC %60, CT %40; and CC %60 CT %35 TT %5 for patients and healthy controls respectively. As a result, it is found that the MTHFR 677TT genotype has protective effect for prostate cancer. 

Anahtar Kelimeler

MTHFR C677T, prostate cancer, polymorphism

HATAY İLİ’NDE MTHFR C677T TEK NÜKLEOTİT POLİMORFİZMİ VE PROSTAT KANSERİ ARASINDAKİ İLİŞKİNİN DEĞERLENDİRİLMESİ

Öz

MTHFR (Metilentetrahidrofolatredüktaz), folat metabolizması ve DNA sentez yolağındaki kilit rolü sebebiyle en önemli enzimlerden biridir. Enzimi kodlayan gendeki C677T tek nükleotid polimorfizmi, prostat kanseri de dahil olmak üzere birçok hastalıkla ilişkilendirilmiştir. Çalışmanın amacı, ilgili polimorfizmin, prostat kanseri teşhisi konmuş hasta ve sağlıklı kontrol bireyler arasında kıyaslanarak, hastalık ile ilişkisinin değerlendirilmesidir. Çalışmaya, 20 prostat kanseri teşhisi konmuş hasta ve herhangi bir patolojisi saptanmamış 20 sağlıklı birey dahil edilmiştir. İlk olarak, bu bireylerden alınan kan örneklerinden DNA’ları izole edildi. İlgili polimorfizmin bulunduğu bölge Polimeraz Zincir Reaksiyonu (PCR) ile çoğaltıldıktan sonra, uygun restriksiyon enzimi aracılığıyla, Restriksiyon Parça Uzunluk Polimorfizmi (RFLP) yöntemi ile kesildi. Daha sonra Poliakrilamid Jel Elektroforezi tekniği ile örnekler yürütüldü ve jel görüntülenerek oluşan bantlar yorumlandı. Sonuçlar, MTHFR C677T polimorfizm genotipleri açısından değerlendirildiğinde, çalışmaya dâhil ettiğimiz hasta bireylerin %60’inde CC (homozigot normal), %40’inde CT (heterozigot mutant); sağlıklı bireylerin ise %60’ında CC, %35’inde CT ve %5’inde TT (homozigot mutant) genotipi olduğu tespit edilmiştir.
Sonuç olarak, MTHFR 677TT genotipinin prostat kanseri için koruyucu etki gösterdiği tespit edilmiştir.

Anahtar Kelimeler

MTHFR C677T, prostat kanseri, polimorfizm

Kaynakça

• - Molloy AM. Genetic aspects of folate metabolism. Subcell Biochem. 2012; 56, 105-30.
• - Chai AU, Abrams J. Homocysteine: a newcardiac risk factor? Clin Cardiol. 2001; 24: 80-84.
• - Guilliams TG. Homocysteine a risk factor for vascular diseases: Guidelines for the clinical practice. JANA. 2004; 7(1): 11-24.
• - Medina MA, Amores-Sanchez MI. Genetic basis of hyperhomocysteinemia. Mol Genet Metab. 2000; 71: 478-480.
• - Lewis SJ, Zammit S, Gunnell D, Smith GD. A meta-analysis of the MTHFR C677T polymorphism and schizophrenia risk. Am J Med Genet B Neuropsychiatr Genet. 2005; 5; 135B(1), 2-4.
• - Langevin SM, Lin D, Matsuo K,Gao CM, Takezaki T, Stolzenberg-Solomon RZ, Vasavi M, Hasan Q, Taioli E. Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer. Toxicol Lett. 2009; 30; 184(2): 73-80.
• - Dong X, Wu J, Liang P, Li J, Yuan L, Liu X. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer: a meta-analysis. Arch Med Res. 2010; 41(2): 125-33.
• - Zhang J, Qiu LX, Wang ZH, Wu XH, Liu XJ, Wang BY, Hu XC. MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls. Breast Cancer Res Treat. 2010; 123(2): 549-55.
• - Yin M, Dong L, Zheng J, Zhang H, Liu J, Xu Z. Meta-analysis of the association between MTHFR C677T polymorphism and the risk of congenital heart defects. Ann Hum Genet. 2012; 76(1): 9-16.
• - Zhang WB, Zhang JH, Pan ZQ, Yang QS, Liu B. The MTHFR C677T Polymorphism and Prostate Cancer Risk: New Findings from a Meta-analysis of 7306 Cases and 8062 Controls. Asian Pacific Journal of Cancer Prevention. 2012; 13(6): 2597-604. 11- Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010; 15;127(12): 2893-917.
• - Arıca S, Nazlıcan E, Özer C, Şilfeler DB, Arıca V, Özgür T, Özaydın Ü. The frequency and distribution of cancer cases in Hatay District in 2008. Journal of Clinical and Experimental Investigations. 2011; 2 (2): 192-195.
• - Kobayashi LC, Limburg H, Miao Q, Woolcott C, Bedard LL, Massey TE, Aronson KJ. Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions. Front Oncol. 2012; 14; 2: 100.
• - Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215.
• - Izmirli M, Inandiklioglu N, Abat D, Alptekin D, Demirhan O, Tansug Z, Bayazit Y. MTHFR Gene Polymorphisms in Bladder Cancer in the Turkish Population. Asian Pacific Journal of CancerPrevention, 2011; Vol 12.
• - Küçükhüseyin Ö, Kurnaz Ö, Akadam-Teker AB, Narter F, Yılmaz-Aydoğan H, İsbir T. Effects of the MTHFR C677T polymorphism on prostate specific antigen and prostate cancer. Asian Pac J Cancer Prev. 2011; 12(9): 2275-8. 17- Muslumanoglu MH, Tepeli E, Demir S, Uludag A, Uzun D, Atli E, Canturk KM, Ozdemir M, Turgut M. The analysis of the relationship between A1298C and C677T polymorphisms of the MTHFR gene with prostate cancer in Eskisehir population. Genet Test Mol Biomarkers. 2009; 13(5): 641-5.
• - López-Cortés A, Jaramillo-Koupermann G, Muñoz MJ, Cabrera A, Echeverría C, Rosales F, Vivar N, Paz-y-Miño C. Genetic polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) genes associated with pathological characteristics of prostate cancer in the Ecuadorian population. Am J Med Sci. 2013; 346(6): 447-54.
• - Jackson MD, Tulloch-Reid MK, McFarlane-Anderson N, Watson A, Seers V, Bennett FI, Egleston B, Ragin C. Complex interaction between serum folate levels and genetic polymorphisms in folate pathway genes: biomarkers of prostate cancer aggressiveness. Genes Nutr. 2013; 8(2): 199-207.
• - Wu HC, Chang CH, Tsai RY, Lin CH, Wang RF, Tsai CW, Chen KB, Yao CH, ChiuCF, Bau DT, Lin CC. Significant association of methylene tetra hydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in taiwan. Anticancer Res. 2010; 30(9): 3573-7.
• - Safarinejad MR, Shafiei N, Safarinejad S. Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C and G1793A) gene and risk of prostate cancer: a case-control study. Prostate. 2010; 1; 70(15): 1645-57. 22- Kimura F, Franke KH, Steinhoff C, Golka K, Roemer HC, Anastasiadis AG, Schulz WA. Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma. Prostate. 2000; 45,225-31. 23- Heijmans BT, Boer JM, Suchiman HE, Cornelisse CJ, Westendorp RG, Kromhout D, Feskens EJ, Slagboom PE. A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Re. 2003; 63,1249-53