Department of Gastroenterology, Zhong Shan Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.
Diagn Pathol. 2009 Nov 24;4:39. doi: 10.1186/1746-1596-4-39.
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate. The non-synonymous single nucleotide polymorphism (nsSNP), C677T (Ala>Val, rs1801133), has been verified to impair enzyme activity. The association with cancer susceptibility, including hepatocellular carcinoma (HCC), has also been widely studied. The results, however, were inconsistent. To shed light on the influence of MTHFR C677T polymorphism on HCC, a meta-analysis was conducted.
The meta-analysis of C677T consisted of 10 studies (1814 cases/2862 controls). The association was measured by using random-effect (RE) or fixed-effect (FE) odds ratio (OR) combined with 95% confidence intervals (CIs) according to the studies' heterogeneity.
Using genetic model analysis, C677T polymorphism was found to increase the risk of HCC in a complete overdominant model, which indicates that heterozygotes CT are at a lesser risk of HCC than either homozygotes CC or TT. Meta-analyses of the 10 studies showed that the TT genotype increased the risk of HCC as compared to the CT genotype: FE OR was 1.20 (95%CI: 1.00-1.45, p for heterogeneity = 0.21). When subgroup analysis was done between the HCC cases and the chronic liver disease (CLD) patients of four studies, meta-analysis showed that individuals with the TT genotype had increased HCC risk compared with those with the CT genotype: FE OR (TT vs. CT) reached 1.81 (1.22-2.71, p for heterogeneity = 0.25). Meanwhile, the C677T polymorphism also increased HCC risk in a recessive model when cases were compared to CLD patients of four studies: RE OR reached 1.85 (95%CI: 1.00-3.42, p for heterogeneity = 0.06). Overall, there was some extent heterogeneity when analyses were performed in various models. There was no publication bias.
MTHFR C677T polymorphism increased the risk of HCC in an overdominant model, and might be a risk factor for HCC occurrence, especially in CLD patients. The association warranted further studies.
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的关键酶。非同义单核苷酸多态性（nsSNP）C677T（Ala>Val，rs1801133）已被证实会损害酶活性。该 SNP 与癌症易感性的关联，包括肝细胞癌（HCC），也得到了广泛研究。然而，结果并不一致。为了阐明 MTHFR C677T 多态性对 HCC 的影响，进行了荟萃分析。
C677T 的荟萃分析包括 10 项研究（1814 例病例/2862 例对照）。根据研究的异质性，使用随机效应（RE）或固定效应（FE）比值比（OR）结合 95%置信区间（CI）来衡量关联。
使用遗传模型分析，发现 C677T 多态性在完全超显性模型中增加 HCC 的风险，这表明杂合子 CT 比纯合子 CC 或 TT 患 HCC 的风险更低。对 10 项研究的荟萃分析表明，TT 基因型与 HCC 的发生相关：FE OR 为 1.20（95%CI：1.00-1.45，p 异质性=0.21）。当对四项研究的 HCC 病例与慢性肝病（CLD）患者进行亚组分析时，荟萃分析表明，与 CT 基因型相比，TT 基因型的个体 HCC 风险增加：FE OR（TT 与 CT）达到 1.81（1.22-2.71，p 异质性=0.25）。同时，当将病例与四项研究的 CLD 患者进行比较时，C677T 多态性在隐性模型中也增加了 HCC 的风险：RE OR 达到 1.85（95%CI：1.00-3.42，p 异质性=0.06）。总的来说，在各种模型中进行分析时存在一定程度的异质性。没有发表偏倚。
MTHFR C677T 多态性在超显性模型中增加 HCC 的风险，可能是 HCC 发生的危险因素，尤其是在 CLD 患者中。该关联需要进一步研究。
