GASTROİNTESTİNAL SİSTEM KANSERLERİNDE METİLENTETRAHİDROFOLAT REDÜKTAZ GENİ 677C → T POLİMORFİZMİNİN İNCELENMESİ

Year 2006, Volume: 15 Issue: 1, 41 - 45, 01.03.2006

Nazife Taşçıoğlu Serpil Taheri Çetin Saatçi Yusuf Özkul

Abstract

Metilentetrahidrofolat redüktaz (MTHFR) geni folat metobolizmasının anahtar rolü oynayan genlerindendir. MTHFR geninde 677C→T polimorfizmi en yaygın görülen polimorfizimdir. Çalışmamızda gastrointestinal sistem(GİS) kanserli hastalarda;MTHFR geni 677C→T polimorfiziminin araştırılması amaçlandı.Bu amaçla GİS kanserli 64 hastanın (41 kolon ve 23 mide karsinomlu vaka) ve 40 sağlıklı kontrolün periferal kan örnekleri alınarak DNA izolasyonu yapıldı. MTHFR geninde 677C→T polimorfizmi PCR RFLP yöntemi kullanılarak belirlendi. 64 GİS kanserli hastada MTHFR 677CC, 677CT, 677TT genotipleri sırasıyla 26(%41), 31(%48), 7(%11); kontrol grubunda ise 15(%37.5), 23(%57,5), 2(%5) olarak tespit edildi. GİS kanserlerinde MTHFR 677TT(homozigot mutant) genotipi kontrol grubuyla karşılaştırıldığında yaklaşık iki kat artmış olarak bulundu.Sonuçlar Ki Kare testi ile değerlendirildiğinde gruplar arasında anlamlı fark bulunamadı(P>0,05) Gruplar arası farkın istatistiksel anlam ifade etmemesinin çalışma gurubunun küçüklüğünden kaynaklandığı dolayısıyla MTHFR 677C→T polimorfizminin GİS kanserlerinde önemli olabileceği düşünülmüştür. Sonuç olarak; geniş hasta grubuna sahip ileri çalışmalarda bu gen polimorfizminin araştırılmasının gerektiği kanısındayız

Keywords

MTHFR, 677 C→T, PCR, GİS

The Investigation of Methylenetetrahydrofolate Reductase Gene 677 C → T Polymorphism in Gastrointestinal Cancer

Abstract

Methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in folate metabolism. The most common polymorphism in MTHFR gene is 677C→T substitution. In our study, peripheral blood samples were obtained from 64 Gastrointestinal (GIS) cancer (41 colon and 23 stomach cancers) cases and 40 healthy controls and DNA was extracted from these samples. MTHFR 677C→ T variant allele was determined by PCR-RFLP assay. Frequencies of MTHFR 677CC, 677CT and 677TT genotypes were 26 (%41), 31 (%48) and 7 (%11) in the GIS cancer’s cases and 15 (%37,5), 23 (%57,5) and 2 (%5) in the controls. MTHFR 677TT (homozygous) genotype was found approximately two fold increased in GIS cancers when compared with control group. However, no significant difference were found between these groups according to Chi Square test (p>0,05). It is thought that differences between these groups don’t mean statistical value due to insufficient number of subjects. Therefore, MTHFR 677C→T polymorphism can be very important in GIS carcinomas. As a conclusion, we think there is a need for research of this polymorphism in larger populations

Keywords

MTHFR, folate, PCR, GIS

References

• Eicholzer M, Luthy Z, Moser V, et al. Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Wkly 2001,131: 539-549.
• Sharp L, Little J. Polymorphism in genes in- volved in folate metabolism and colorectal neoplasia. Am J Epidemiol 2004, 159: 423- 443.
• Virich CM, Kampman E, Bigler J, Schwartz SM, Chen C, et al. Lack of association be- tween the C677T MTHFR polymorphism and colorectal hyperplastic polyps. Cancer Epide- miol Biomarkers Prev 2000, 9: 427-433.
• Gayette P, Par A, Milas R, Frasst P, Tran P, et al. Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mammolian genome 1998, 9: 652- 656.
• Carmet R, Gren R, Rosenblatt DS, Watkins D. Update on cobalamin, folate and hemocys- teine. Am Society of Hem 2003,62-81.
• S k i b o l a C F , S m i t h M T , K a n e E , etal.Polimorphisms in the methylenetetrahy- drofolate reductase gene are associated with susceptibilitiy to acute leukemia in adults.Proc Natl Acad Sci USA 1999,96 (22):12216-8.
• Keku T, Millikan R, Worley K,et al. 5-10- Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphısms and colon can- ser in african americans and whites. Canser Epidomiol Bio makers and Prev 2002, 11:1611-1621.
• De Jong M M, Nolte I M, de Meerman GJ, et al. Low-penerance genes and their involve- ment in colorectal cancer susceptibility. Can- ser Epdemiol Bio markers and and Prev 2002, 11: 1332-1352.
• Arthur S, Schneider MD, Philip A, Seanto MD, Patoloji (2.Baskı), Nobel Tıp Kitabev- leri ,Ankara,2001, 227-239.
• Song C, Xing D, Tan W, Wel Q, Lin D, Me- thylenetetrahydrofolate reductase polymor- phisms increase risk of esophageal squamous cell carcinoma in a chinese population. Can- cer Reasearch 2001,61: 3272-3275.