MTHFR基因C677T和A1298C多态与贲门癌的遗传易感性  

Single nucleotide polymorphisms in methylenetetrahydrofolate reductase gene and susceptibility to cancer of the gastric cardia in Chinese population

作　　者：缪小平[1] 邢德印[1] 谭文[1] 吕文富[1] 林东昕[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所病因及癌变研究室,北京100021

出　　处：《中华医学杂志》2002年第10期669-672,共4页National Medical Journal of China

基　　金：国家杰出青年科学基金 (3 982 5 12 2 ) ;国家"九五"医学重点科技攻关项目 (9690 60 10 6)

摘　　要：目的　探讨代谢叶酸的亚甲基四氢叶酸还原酶 (MTHFR)基因单核苷酸多态与贲门癌风险的关系。方法　以聚合酶链反应和限制性片段长度多态方法 ,分析了 2 0 5个贲门癌病人和性别、年龄配对的 36 0个正常对照的MTHFR基因C6 77T和A12 98C基因型及其对贲门癌风险的相关性。结果　在正常对照中 ,MTHFR 6 77CC、CT、TT基因型频率分别为 35 0 %、4 7 8%和 17 2 % ,而在贲门癌病人中分别为 2 0 5 %、5 0 7%和 2 8 8% (χ2 =17 6 3,P =0 0 0 0 2 )。多因素分析发现 ,携带 6 77CT或 6 77TT基因型的个体发生贲门癌的风险比 6 77CC基因型分别高 1 76倍 (95 %可信区限 1 13～ 2 76 )和 2 97倍 (95 %可信区限 1 75～ 5 0 5 )。MTHFRA12 98C基因型在病例和对照中的分布差异无显著性意义(χ2 =0 0 8,P =0 96 ) ,但 12 98变异基因型与 6 77变异基因型之间有协同作用。携带MTHFR 6 77CT/12 98CC基因型个体发生贲门癌的风险是携带MTHFR 6 77CC/ 12 98AA基因型个体的 17倍 (95 %可信区限 1 2 6～无穷大 )。结论　MTHFR单核苷酸多态是中国人贲门癌的遗传易感性因素。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 frenquency of 677TT was 17 2% among the controls and 28 8% among the AGC patients %(χ 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 (χ 2=0 08, P =0 96). The value of odd ratio (OR) in the individuals with 677CT//1298AA genotype (95% CI, 1 48～6 48), and the value of OR in the individuals with 677CT/1298CC genotype was 17 00 (95% CI, 1 26～∞; 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.

关 键 词：MTHFR基因 C677T A1298C 贲门癌 遗传易感性 基因多态性 

分 类 号：R735.2[医药卫生—肿瘤]