胃癌组织中叶酸水平与代谢酶亚甲基四氢叶酸还原酶基因多态性的关系研究

Relationship between folate and methylenetetrahydrofolate reductase polymorphisms in human gastric cancer tissues

目的 探讨人胃癌组织中叶酸水平与代谢酶亚甲基四氢叶酸还原酶（MTHFR）基因多态性的变化及其关系.方法 收集38例晚期胃癌患者的癌区、癌旁和外周正常区域组织标本,以自动化学发光系统测定人胃癌组织叶酸含量,PCR-限制性内切酶片段长度多态性技术检测MTHFR基因677（C→T）和1298（A→C）两个常见多态,并以34例慢性浅表性胃炎（CSG）组织作为对照,分析叶酸、MTHFR基因多态性的变化及其关系.结果 CSG对照组中叶酸含量[（5.48±2.15）ng/m1]明显高于胃癌组织[癌区（3.65±1.97）ng/ml,癌旁（4.01±2.11）ng/ml,外周正常组织（4.00±2.20）ng/ml],胃癌组织MTHFR基因的两个多态位点中,677CT基因型叶酸含量最高,而1298（A→C）多态则未见明显差异.677TT基因型与CC基因型相比有减少胃癌发生的趋势,但与其生物学行为关系不密切.677TT基因型高叶酸组与CC基因型低叶酸组相比发生胃癌的相对风险度为0.11（95%CI：0.01～1.02）.癌组织标本检测中未发现1298CC基因型.结论 组织叶酸含量降低者发生胃癌风险明显增加.MTHFR基因多态性并不是胃癌的一个孤立危险因素,它和组织叶酸含量共同作用于胃癌发生.

Objective To investigate the changes of folate and methylenetetrahydrofolate reductase （MTHFR） polymorphisms in human gastric cancerous, para-cancerous and non-cancerous tissues and the relationship between them. Methods Folate concentration in gastric cancer tissues from 38 patients with advanced gastric cancer was detected by automated chemiluminescence system. Two common polymorphisms [677（C→T） and 1298（A→C）]of MTHFR gene were analyzed by PCR-RFLP. The tissues from 34 patients with chronic superficial gastritis（CSG） were used as controls. Results Folate concentration in CSG [（5.48±2. 15）ng/ml]was significantly higher than in cancerous [（3.65±1.97）ng/ml], para cancerous [ （4. 01 ± 2.11 ） ng/ml], and non-cancerous [ （4.00 ± 2. 20） ng/ml] tissues. Folate concentration was highest in tissues with genotype 677CT, while there was no difference among the tissues with three genotypes of 1298 polymorphism. The genotypes of 677TT had a lower trend toward an increase in risk of gastric cancer compared with 677CC , but was not associated with biological characters. Higher folate group with 677TT genotype had an decreased risk for developing gastric cancer compared with the lower folate group with 677CC genotype （ OR= 0.11;95% CI=0.01-1.02）. The genotype of 1298CC was not found in gastric cancer tissues. Conclusions Lower folate in gastric tissues is associated with higher risk of gastric cancer. MTHFR gene polymorphisms are not an isolated risk factor for developing gastric cancer , but may act together with folate concentration.