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首页> 外文期刊>International journal of colorectal disease. >Role of MTHFR polymorphisms and folate levels in different phenotypes of sporadic colorectal cancers.
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Role of MTHFR polymorphisms and folate levels in different phenotypes of sporadic colorectal cancers.

机译：MTHFR多态性和叶酸水平在散发性结直肠癌不同表型中的作用。

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BACKGROUND AND AIMS: By altering both DNA methylation and nucleotide synthesis, folate metabolism is thought to contribute to colorectal carcinogenesis. We examined the role of folate metabolism in three different phenotypes of sporadic colorectal cancers (CRCs), phenotypes that were classified by the status of microsatellite instability (MSI) and chromosomal instability (CIN): MSI-H, microsatellite stability (MSS)/aneuploidy, and MSS/diploid. PATIENTS AND METHODS: A total of 195 sporadic colorectal tumors and another 195 age- and gender-matched healthy volunteers in Taipei-Veteran General Hospital and Taipei City Hospital were collected. We analyzed for MTHFR (methylenetetrahydrofolate reductase) polymorphisms (C677T, A1297C), folate, and vitamin B(12) levels. We determined MSI status and DNA ploidy with fluorescent polymerase chain reaction and flow cytometry. Relations between clinicopathological variables and molecular variables were analyzed by chi (2) tests (with Yates' correction) for categorical variables and Student's t test for numerical variables. RESULTS: Folate levels (5.02+/-4.43 ng/ml) were significantly lower in cancer patients than in controls (7.22+/-4.46 ng/ml). Vitamin B(12) level was similar between cancer patients and controls. The frequency of the TT genotype of MTHFR C627T (12.3%) was slightly higher than controls (8.2%), but it did not reach statistical significance (p=0.174). Within the low-folate group (<5 ng/ml), the frequency of the TT genotype in cancer patients (14.4%) was significantly higher than in controls (4.6%). Sixteen patients who had MSI-H CRC (8.2%) had a significantly higher frequency of TT MTHFR (37.5%) and lower folate levels (3.56+/-2.41 ng/ml) than patients with MSS tumors (10.1%, 5.14+/-3.72 ng/ml). Patients with MSS/aneuploid tumors had significantly lower folate levels (4.50+/-3.06 ng/ml) than those with MSS/diploid tumors (6.69+/-4.73 ng/ml). CONCLUSION: Folate deficiency and the MTHFR genetic polymorphism play an important role in colorectal carcinogenesis, including MSI and CI. SYNOPSIS: Folate metabolism plays an important role in colorectal carcinogenesis. We demonstrate that patients with MSI-H tumors had higher frequency of TT MTHFR C627T (37.5%), and patients with MSS/aneuploid tumor had lower folate level (4.50+/-3.06 ng/ml).
机译：背景与目的：通过改变DNA甲基化和核苷酸合成，叶酸代谢被认为有助于大肠癌的发生。我们研究了叶酸代谢在散发性结直肠癌（CRC）的三种不同表型中的作用，这些表型按微卫星不稳定性（MSI）和染色体不稳定性（CIN）的状态分类：MSI-H，微卫星稳定性（MSS）/非整倍性，以及MSS /二倍体。患者与方法：收集了台北老总医院和台北市立医院的195例散发性结直肠肿瘤以及195例年龄和性别相匹配的健康志愿者。我们分析了MTHFR（亚甲基四氢叶酸还原酶）多态性（C677T，A1297C），叶酸和维生素B（12）的水平。我们通过荧光聚合酶链反应和流式细胞仪确定了MSI状态和DNA倍性。通过卡氏（2）检验（采用Yates校正）和分类变量的学生t检验，分析了临床病理变量和分子变量之间的关系。结果：癌症患者的叶酸水平（5.02 +/- 4.43 ng / ml）显着低于对照组（7.22 +/- 4.46 ng / ml）。癌症患者和对照组之间的维生素B（12）水平相似。 MTHFR C627T TT基因型的频率（12.3％）略高于对照组（8.2％），但未达到统计学意义（p = 0.174）。在低叶酸组（<5 ng / ml）中，癌症患者的TT基因型频率（14.4％）显着高于对照组（4.6％）。 16例MSI-H CRC患者（8.2％）比MSS肿瘤患者（10.1％，5.14 + /）具有更高的TT MTHFR频率（37.5％）和更低的叶酸水平（3.56 +/- 2.41 ng / ml）。 -3.72 ng / ml）。 MSS /非整倍性肿瘤患者的叶酸水平（4.50 +/- 3.06 ng / ml）显着低于MSS /二倍体肿瘤（6.69 +/- 4.73 ng / ml）。结论：叶酸缺乏和MTHFR基因多态性在大肠癌的发生中起着重要作用，包括MSI和CI。简介：叶酸代谢在结直肠癌的发生中起重要作用。我们证明，患有MSI-H肿瘤的患者发生TT MTHFR C627T的频率更高（37.5％），而患有MSS /非整倍体肿瘤的患者叶酸水平较低（4.50 +/- 3.06 ng / ml）。

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