Department of Biomedical Technology, National Research Center, Cairo, Egypt.
Cancer Biomark. 2009;5(6):233-40. doi: 10.3233/CBM-2009-0108.
The study was planned as a pilot study to investigate two common polymorphisms in the MTHFR gene c.677C > T and c.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 Venous blood samples were withdrawn from 35 cases of CRC and 68 healthy controls.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. 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). Frequencies of heterozygous and homoyzgous polymorphisms of MTHFR at positions 677 and 1298 in carcinoma tissues were always the highest. At position 677, TT 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 MTHFR 1298CC + 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 1298AA, 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%CI 0.94-21.56], OR 3.12 [95%CI 0.79-12.36] and OR 18 [95%CI 1.56-207.5], 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.
这项研究旨在调查 MTHFR 基因 c.677C>T 和 c.1298A>C 这两种常见的多态性及其与埃及人群结直肠癌（CRC）风险增加的相关性。从 35 例 CRC 患者和 68 例健康对照者中抽取静脉血样本。所有病例均获得结直肠腺癌组织和无癌组织标本。CRC 肿瘤组织中 MTHFR677T 和 1298C 等位基因的频率明显高于 CRC 患者的种系等位基因（分别为 50%和 56%）和健康对照者（分别为 33%和 41%）。MTHFR 在位置 677 和 1298 的杂合子和纯合子多态性的频率在癌组织中总是最高的。在位置 677，TT 和 CT 基因型频率分别为 17%和 66%，比值比（OR）为 11 [95%置信区间（CI）2.39-50.59]和 8.34 [95%CI 2.97-23.92]，在癌组织中。而在患者的种系中，677TT 和 CT 的基因型频率分别为 6%和 54%，OR 为 1.57 [95%CI 0.26-9.51]和 2.99 [95%CI 1.25-7.12]，与对照组（分别为 6%和 29%）相比。MTHFR 1298CC+AC 联合基因型频率在癌组织中为 86%，OR 为 3.71 [95%CI 1.28-10.78]，在患者的种系中为 69%，OR 为 1.35 [95%CI 0.57-3.21]，在对照组中为 62%。比较患者的种系 DNA 多态性与对照组外周血 DNA，677CT 加任何以下基因型（1298AA、AC 或 CC）的联合基因型均可增加 CRC 的风险，OR 为 4.5 [95%CI 0.94-21.56]、OR 为 3.12 [95%CI 0.79-12.36]和 OR 为 18 [95%CI 1.56-207.5]，提示埃及人群对 CRC 有强烈的遗传易感性。这些结果表明，至少一个 MTHFR 基因 677C>T 多态性需要显著增加 CRC 发展的风险。需要进一步的大规模研究来证实目前的发现。
