[亚甲基四氢叶酸还原酶基因单核苷酸多态性与中国人群贲门癌易感性]
[Single nucleotide polymorphisms in methylenetetrahydrofolate reductase gene and susceptibility to cancer of the gastric cardia in Chinese population].
作者信息
Miao Xiaoping, Xing Deyin, Tan Wen, Lu Wenfu, Lin Dongxin
机构信息
Department of Etiology & Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
出版信息
Zhonghua Yi Xue Za Zhi. 2002 May 25;82(10):669-72.
OBJECTIVE
To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism that affects DNA methylation and synthesis, and the risk of adenocarcinoma of the gastric cardia (AGC).
METHODS
Genomic DNA was isolated from the peripheral lymphocytes of 205 patients with AGC and 360 age-and-sex-matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR genes C6677T and A1298C and the relation between these genotypes and risk of AGC was analyzed.
RESULTS
The genotype frequency of MTHFR C677CC was 35.0% among the controls and was 20.5% among the AGC patients; the genotype frequency of 677CT was 47.8% among the controls and 50.7% among the AGC patients, and the genotype frequency of 677TT was 17.2% among the controls and 28.8% among the AGC patients % (chi(2) = 17.63, P = 0.0002). The individuals with 677CT genotype or 677TT genotype had a 1.76-fold [95% confidence interval (CI), 1.13 - 2.76] or 2.97-fold (95% CI, 1.75 - 5.05) increased risk of developing AGC compared with those who had 677CC genotype. The distribution of MTHFR A1298C genotype was not significantly different between the two groups (chi(2) = 0.08, P = 0.96). The value of odd ratio (OR) in the individuals with 677CT//1298AA genotype (95% CI, 1.48 approximately 6.48), and the value of OR in the individuals with 677CT/1298CC genotype was 17.00 (95% CI, 1.26 approximately infinity; P = 0.042).
CONCLUSION
Single nucleotide polymorphism in the MTHFR gene is a risk factor of carcinogenesis of AGC in the Chinese population. Although the MTHFR A1298C polymorphism was not associated with AGC, The risk of developing AGC in the individuals with MTHFR677CT/1298CC was 17 times higher than that in the individuals with MTHFR677CC/1298AA, thus showing that a joint effect exists between the MTHFR 677 and 1298 polymorphisms on the risk of AGC.
目的
探讨亚甲基四氢叶酸还原酶（MTHFR）基因多态性与贲门腺癌（AGC）发病风险的关系。MTHFR是叶酸代谢中的关键酶，影响DNA甲基化和合成。
方法
收集205例AGC患者及360例年龄、性别匹配的对照者外周血淋巴细胞，提取基因组DNA，采用聚合酶链反应和限制性片段长度多态性技术检测MTHFR基因C6677T和A1298C多态性，并分析其与AGC发病风险的关系。
结果
对照组中MTHFR C677CC基因型频率为35.0%，AGC患者中为20.5%；对照组中677CT基因型频率为47.8%，AGC患者中为50.7%；对照组中677TT基因型频率为17.2%，AGC患者中为28.8%（χ² = 17.63，P = 0.0002）。与677CC基因型相比，677CT基因型或677TT基因型个体发生AGC的风险分别增加1.76倍[95%置信区间（CI），1.13 - 2.76]和2.97倍（95%CI，1.75 - 5.05）。两组间MTHFR A1298C基因型分布差异无统计学意义（χ² = 0.08，P = 0.96）。677CT//1298AA基因型个体的比值比（OR）值为（95%CI，1.48～6.48），677CT/1298CC基因型个体的OR值为17.00（95%CI，1.26～∞；P = 0.042）。
结论
MTHFR基因单核苷酸多态性是中国人群AGC发生的危险因素。虽然MTHFR A1298C多态性与AGC无关，但MTHFR677CT/1298CC基因型个体发生AGC的风险是MTHFR677CC/1298AA基因型个体的17倍，提示MTHFR 677和1298位点多态性对AGC发病风险存在联合作用。
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