Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, PR China.
State key laboratory of cancer biology and Xijing hospital of digestive diseases, The Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
Clin Res Hepatol Gastroenterol. 2014 Apr;38(2):172-80. doi: 10.1016/j.clinre.2013.10.002. Epub 2013 Dec 6.
Several studies have indicated an association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and the risk of hepatocellular carcinoma (HCC). However, the conclusions are inconsistent. Therefore, a meta-analysis was performed.
Databases like Pubmed, EMBASE, and EBSCO (up to September 2012) were searched to retrieve case-control trials about MTHFR (C677T or A1298C) polymorphisms and HCC. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria. Data were extracted and analyzed by software STATA 11.0.
Nine studies were included with 10 datasets and 5132 cases. C677T polymorphism was associated with HCC risk in a heterozygous model (TT vs. CT: OR=1.20, 95% CI: 1.02-1.40). For the A1298C polymorphism, a significantly decreased HCC risk was found in the dominant, heterozygous and homozygous models (CC vs. AA+AC: OR=0.52, 95% CI: 0.33-0.80; CC vs. AC: OR=0.50, 95% CI: 0.32-0.79; CC vs. AA: OR=0.52, 95% CI: 0.33-0.81). Subgroup analysis stratified by ethnicity and type of control further indicated decreased HCC risks in Asians (CC vs. AA+AC: OR=0.47, 95% CI: 0.26-0.84; CC vs. AC: OR=0.41, 95% CI: 0.24-0.71; CC vs. AA: OR=0.46, 95% CI: 0.27-0.78), studies with controls of healthy people (CC vs. AA: OR=0.54, 95% CI: 0.31-0.93; CC vs. AC: OR=0.54, 95% CI: 0.31-0.94; CC vs. AA+AC: OR=0.55, 95% CI: 0.32-0.94), and controls of non-HCC patients (CC vs. AC: OR=0.43, 95% CI: 0.19-0.96).
Homozygous carriers of MTHFR C677T mutation are more susceptible to HCC, but homozygous mutations of MTHFR A1298C may play a protective role for developing HCC.
几项研究表明，亚甲基四氢叶酸还原酶（MTHFR）基因多态性与肝细胞癌（HCC）的风险之间存在关联。然而，结论并不一致。因此，进行了荟萃分析。
检索 Pubmed、EMBASE 和 EBSCO 等数据库（截至 2012 年 9 月），以获取有关 MTHFR（C677T 或 A1298C）多态性与 HCC 的病例对照研究。两位研究人员根据纳入和排除标准独立筛选文献。使用 STATA 11.0 软件提取和分析数据。
纳入了 9 项研究，共 10 个数据集，5132 例病例。C677T 多态性与 HCC 风险在杂合子模型中相关（TT 与 CT：OR=1.20，95%CI：1.02-1.40）。对于 A1298C 多态性，在显性、杂合子和纯合子模型中均发现 HCC 风险显著降低（CC 与 AA+AC：OR=0.52，95%CI：0.33-0.80；CC 与 AC：OR=0.50，95%CI：0.32-0.79；CC 与 AA：OR=0.52，95%CI：0.33-0.81）。按种族和对照类型进行的亚组分析进一步表明，亚洲人群 HCC 风险降低（CC 与 AA+AC：OR=0.47，95%CI：0.26-0.84；CC 与 AC：OR=0.41，95%CI：0.24-0.71；CC 与 AA：OR=0.46，95%CI：0.27-0.78），对照为健康人群（CC 与 AA：OR=0.54，95%CI：0.31-0.93；CC 与 AC：OR=0.54，95%CI：0.31-0.93；CC 与 AA+AC：OR=0.55，95%CI：0.32-0.94），对照为非 HCC 患者（CC 与 AC：OR=0.43，95%CI：0.19-0.96）。
MTHFR C677T 突变的纯合子携带者更容易患 HCC，但 MTHFR A1298C 的纯合子突变可能对 HCC 的发生起保护作用。
