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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 To investigate the relationship between polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and the risk of primary liver cancer in Chinese population and its association with risk factors. METHODS: Population-based case-control studies included 204 newly diagnosed cases of primary hepatocellular carcinoma and 415 healthy controls. The genetic polymorphisms of MTHFR C677T and A1298C were analyzed by PCR-RFLP. Results The frequency of MTHFR C / C, C / T and T / T genotypes were 25.8%, 58.8% and 15.5% respectively in the cases and 34.5%, 50.9% and 14.6% respectively in the control cases. Individuals with the Any T genotype had a risk of liver cancer of 1.58 (95% CI: 1.01-2.48) compared with C / C genotypes, and the proportion of MTHFR1298 genotypes in healthy controls was 69.7% ( A / A), 28.4% (A / C) and 1.8% (C / C) respectively. There was no significant difference in frequency distribution between case group and control group. The risk of liver cancer in individuals carrying both the MTHFR 677 Any T and 1298 Any C genotypes increased to 2.05 (95% CI: 0.96-4.36). The combination of MTHFR677 polymorphism with the three major risk factors for hepatocellular carcinoma (hepatitis B, Water, Moldy Food Intake) analysis found that individuals with the MTHFR-high-risk gene (Any T genotype) had a high risk of liver cancer among all exposure groups for different risk factors. Individuals who were simultaneously exposed to three major risk factors and carrying high-risk genotypes adjusted for the risk of liver cancer to 71.69. Conclusion The genetic polymorphism of MTHFR C.677T is associated with the risk of liver cancer and may be combined with other environmental risk factors to affect the risk of liver cancer.