الفهرس 
Genetic factors predisposing to CRC
Relation between folate and CRCOnly 14 pages are availabe for public view
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Abstract
Name: Hanan Abd Alla Abdel Menem
Title: A study on genetic mutation within the human methylenetetrahydrofolate reductase (MTHFR) gene in cases of colorectal carcinoma in Egypt.
Ph.D.Thesis, Ain Shams University, Faculty of Science, Biochemistry Department, 2009.
MTHFR is the enzyme responsible for the reduction of methylenetetrahydrofolate, a key single-carbon donor in nucleotide synthesis and the methylation of DNA. In this pilot study we investigated two common polymorphisms in the MTHFR gene 677C→T and 1298A→C and their association with enhanced risk of colorectal cancer (CRC) in a sample of Egyptian individuals. Venous blood samples were withdrawn from 35 cases of CRC and 68 healthy controls. Specimens from colonic and rectal carcinoma tissues in addition to cancer free tissues were obtained from all cases. Polymorphisms was studied by RFLP analysis and confirmed by SSCP analysis using Hot SSCP (~1200 Ci/m mol α d ATP S35) and cold SSCP. Frequencies of MTHFR677T and 1298C alleles were significantly higher among cases of CRC tumor tissues (50% and 56%, respectively) than germ line alleles in CRC patients (33% and 41%, respectively) and healthy controls (21% and 35%, respectively). Heterozygous and homozygous polymorphism frequencies of MTHFR at positions 677 and 1298 in carcinoma tissues were always the highest. At position 677TT and CT genotype frequencies were 17% and 66% with an odds ratio {OR} of 11[95% confidence interval {CI} 2.39-50.59] and OR 8.34 [95%CI 2.97 -23.92], respectively, in carcinoma tissues. While in the germ line of patients the genotype frequencies of 677TT and CT were 6% and 54% with OR 1.57 [95%CI 0.26-9.51] and 2.99 [95%CI 1.25 -7.12], respectively, compared to controls (6% and 29%, respectively). The combined genotype MTHFR1298 CC+AC frequencies were 86% with OR 3.71 [95%CI 1.28-10.78] in carcinoma tissues, 69% with OR 1.35 [95%CI 0.57-3.21] in germ line of patients and 62% in controls.The combined genotype 677CT plus any of the following genotypes 1298 AA, AC or CC enhanced risk of CRC, when comparing germ line DNA polymorphism of patients versus peripheral blood DNA of control subjects with OR 4.5[95%CI0.94-21.56], OR 3.12 [95%CI 0.79-12.36] and OR 18 [95% CI1.56-207.5], respectively, suggesting strong genetic predisposition of certain Egyptian population to CRC. These results suggested that at least one C to T polymorphism at 677MTHFR gene is required to significantly increase the risk for CRC development. Further large scale studies are required to confirm the present findings