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首页> 外文期刊>World Journal of Gastroenterology >Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis.
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Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis.

机译:黏膜组织中的叶酸水平与亚甲基四氢叶酸还原酶多态性无关,但与胃癌发生有关。

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AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation. METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls. Folate concentrations in these tissues were detected by the FOL ACS:180 automated chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP). RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16(INK4A) in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21(WAF1) in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype. CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesis through hypomethylation and overexpression of c-myc.
机译:目的:评估粘膜组织中的叶酸水平和一些常见的亚甲基四氢叶酸还原酶(MTHFR)变异体是否与通过DNA甲基化引起的胃癌风险相关。方法:采用实时荧光定量PCR技术检测38例胃癌患者76例黏膜组织中肿瘤相关基因的表达。来自34例慢性浅表性胃炎(CSG)患者胃镜活检组织的样本用作对照。通过FOL ACS:180自动化学发光系统检测这些组织中的叶酸浓度。通过PCR-RFLP分析MTHFR多态性,并通过甲基化特异性PCR(MSP)确定肿瘤相关基因的启动子甲基化。结果:CSG中的叶酸浓度显着高于癌组织。 c-myc的表达降低和甲基化伴随着较高的叶酸浓度。具有MTHFR 677CC的样品中的启动子高甲基化和p16(INK4A)的丢失比具有677TT或677CT基因型的样品中更常见。与存在677CC或677TT时相比,具有MTHFR 677CT的样品中启动子的高甲基化和p21(WAF1)的丢失更为频繁。与677CC基因型相比,677CT基因型显示出较高的胃癌风险。结论:胃黏膜组织中较低的叶酸水平可能通过甲基化不足和c-myc的过表达而增加了胃癌发生的风险。

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