亚甲基四氢叶酸还原酶基因多态性与肝癌关系探讨

Exploration on the relationship between MTHFR(5,10-methylenetetrahydrofolate rednctase) gene polymorphisms and the risk of primary liver cancer

目的探讨亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)基因多态性与中国人群原发性肝癌危险度的关系,及与危险因素结合对危险度影响。方法以人群为基础的病例对照研究,包括204例确诊的新发原发性肝癌病例以及415例健康对照。MTHFR C677T和A1298C的基因多态性由PCR-RFLP的方法进行分析。结果MTHFR C/C,C/T,T/T基因型的频率在病例中分别为:25.8%,58.8%,15.5%,在对照中分别为34.5%,50.9%,14.6%。和C/C 基因型相比,携带Any T基因型的个体患肝癌的危险度为:1.58(95%CI:1.01-2.48),MTHFR1298各基因型在健康对照中的比例分别为:69.7%(A/A),28.4%(A/C),1.8%(C/C),病例组与对照组频率分布无显著性差异。同时携带MTHFR 677 Any T和1298 Any C基因型的个体肝癌危险度上升到2.05(95%CI:0.96-4.36).结合MTHFR677多态性与肝癌的三大主要危险因素(乙型肝炎、饮生水、霉变食物摄入)分析发现所有不同危险因素的暴露组中,携带MTHFR高危基因(Any T基因型)的个体患肝癌危险度均高。同时暴露于3个主要危险因素并携带高危基因型的个体,调整的肝癌危险度上升到71.69。结论MTHFR C.677T的基因多态性与肝癌危险度有关,且可以与其他环境危险因素结合影响肝癌的危险度。

Objective The purpose of this study was to evaluate the main effect of polymorphisms of MTHFR gene and their possible joint effects with environmental risk factors on the risk of primary liver cancer. Methods A populatlon-based case-control study was conducted in China, including 204 newly diagnosed cases of primary liver cancer and 415 healthy control subjects. Polymorphisms of MTHFR C677T and A1298C were assayed by PCR-RFLP technique. The data were analyzed using the logistic regression model. Results The frequencies of C/C, C/T, T/T genotypes of MTHFR C677T were 25.8%,58.8% and 15.5 % in cases and 34.5% ,50.9% and 14.6% in controls,respectively. The adjusted OR for any T genotype was 1.58 （1.01-2.48） when compared with C/C genotype. The proportions of MTHFR1298 genotype were 69.7%（A/A）, 28.4%（A/C） and 1.8% （C/C） in controls, which is similar with that in liver cancer cases. Individual carrying both any T and any C genotypes will have about 2 times increased risk of primary liver cancer. The study further explored the combined effect of MTHFR C677T polymorphism and three major risk factors （HBV infection,moldy food intake and raw water drinking） of liver cancer and observed increased risks for any T genotype of MTHFR carrier for each exposure group. Among subjects exposed to all three risk factors and with MTHFR variant genotypes, the risk of developing liver cancer was elevated to 71.69. Conclusion In this study,an association between MTHFR 677T variant genotypes and risk of primary liver cancer was suggested. The gene polymorphism in combination with other major risk factors may influence risk of primary liver cancer.