Wang Binfeng, Ma Miaomiao, Guo Xiaojun, Yan Yan, Li Lang
The Renmin Hospital of Tongchuan City, Tongchuan, Shanxi, China.
The Yan'an University, Yan'an, Shanxi, China.
Medicine (Baltimore). 2021 Oct 15;100(41):e27527. doi: 10.1097/MD.0000000000027527.
To evaluate the associations between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and hepatocellular carcinoma (HCC) with meta-analysis and trial sequential analysis.
PubMed, Embase, the Google Scholar, Wan fang database, VIP database, and China National Knowledge Infrastructure were extensively searched before April 2021. Odds ratios (ORs) and 95% confidence interval (95% CI) were calculated. Review Manager Version 5.3, STATA version 12.0 and TSA 0.9.5.10 Beta software were used.
Nineteen studies with 6941 HCC patients and 9436 controls were finally included. The MTHFR rs1801133 (C677T) SNP was associated with increased HCC risk under heterozygote genetic model (OR = 1.10, 95% CI = [1.01, 1.20]). For Subgroup analysis, increased risks of HCC were detected in Mongoloid, Chinese. For MTHFR rs1801131 (A1298C) SNP, increased risk of HCC was only observed in Caucasians (allelic: OR = 1.86, 95% CI = [1.49, 2.31]; homozygote: OR = 3.39, 95% CI = [2.18, 5.27]), interesting decreased risk was detected in Mongoloid (recessive: OR = 0.30, 95% CI = [0.15, 0.58]; homozygote: OR = 0.41, 95% CI = [0.24, 0.72]). Sensitivity analysis indicated stability in our results. Publication bias was not detected based on Begg test and Egger test. Trial sequential analysis indicated further studies to confirm the associations in MTHFR C677T polymorphism.
The MTHFR rs1801133 SNP was associated with an increased risk of HCC in Mongoloid population especially in Chinese. Increased HCC risk is also observed in Caucasian population for the MTHFR rs1801131 SNP, and decreased risk of HCC is remarkably discovered in Mongoloid and Chinese subgroups, which need further validation.
采用荟萃分析和试验序贯分析评估亚甲基四氢叶酸还原酶（MTHFR）单核苷酸多态性（SNP）与肝细胞癌（HCC）之间的关联。
在2021年4月之前广泛检索了PubMed、Embase、谷歌学术、万方数据库、维普数据库和中国知网。计算优势比（OR）和95%置信区间（95%CI）。使用Review Manager 5.3版、STATA 12.0版和TSA 0.9.5.10 Beta软件。
最终纳入19项研究，共6941例HCC患者和9436例对照。在杂合子遗传模型下，MTHFR rs1801133（C677T）SNP与HCC风险增加相关（OR = 1.10，95%CI = [1.01, 1.20]）。亚组分析显示，在蒙古人种、中国人中检测到HCC风险增加。对于MTHFR rs1801131（A1298C）SNP，仅在高加索人群中观察到HCC风险增加（等位基因：OR = 1.86，95%CI = [1.49, 2.31]；纯合子：OR = 3.39，95%CI = [2.18, 5.27]），而在蒙古人种亚组中发现风险降低（隐性：OR = 0.30，95%CI = [0.15, 0.58]；纯合子：OR = 0.41，95%CI = [0.24, 0.72]）。敏感性分析表明结果具有稳定性。基于Begg检验和Egger检验未检测到发表偏倚。试验序贯分析表明需要进一步研究以证实MTHFR C677T多态性的关联。
MTHFR rs1801133 SNP与蒙古人种尤其是中国人患HCC的风险增加相关。对于MTHFR rs1801131 SNP，在高加索人群中也观察到HCC风险增加，而在蒙古人种和中国亚组中显著发现HCC风险降低，这需要进一步验证。
