MTHFR基因C677T位点的基因多态性对中国人群乙型肝炎病毒相关肝细胞癌易感性的影响：一项病例对照研究

Genetic Polymorphism of MTHFR C677T Influences Susceptibility to HBV-Related Hepatocellular Carcinoma in a Chinese Population: a Case-Control Study.

作者信息

Qiao Kunyan, Zhang Shitian, Trieu Congdoanh, Dai Qinghai, Huo Zhixiao, Du Yanan, Lu Wei, Hou Wei

出版信息

Clin Lab. 2017 Apr 1;63(4):787-795. doi: 10.7754/Clin.Lab.2016.161003.

DOI:10.7754/Clin.Lab.2016.161003

PMID:28397480

Abstract

BACKGROUND

Methylene tetrahydrofolate reductase (MTHFR) is the key enzyme of folic acid metabolism and the C677T mutation is associated with decreased enzyme activity. Several studies have shown its regulatory role in carcinogenesis and tumor growth. HBV (hepatitis B virus)-related HCC (hepatocellular carcinoma) is one of the most common liver cancers worldwide. Therefore, the present case-control study aimed to investigate the role of genetic polymorphism of MTHFR C677T in the development and progression of HBV-related HCC in a Chinese population.

METHODS

Subjects enrolled included 204 HBV-related HCC patients and 211 HBV infected patients without HCC. MTHFR C677T polymorphism was genotyped via a DNA microarray-based assay. The relationship between the MTHFR C677T polymorphism and HBV-related HCC was analyzed.

RESULTS

The genotype frequencies of MTHFR C677T were statistically different between the HCC and control groups (p = 0.025). The TT genotype was associated with elevated risk of HBV-related HCC in a Chinese population under different genetic models after an adjustment for age, gender, HBV infection duration, and HCC family history (T vs. C, OR = 1.462, 95% CI: 1.090 - 1.962, p = 0.011; TT vs. CC, OR = 2.151, 95% CI: 1.143 - 4.049, p = 0.018; TT vs. CC+CT, OR = 1.918, 95% CI: 1.215 - 3.026, p = 0.005). When stratified with the known duration of HBV infection, subjects with HBV infection duration of more than 20 years and carrying the homozygous TT genotype had a higher susceptibility to HCC than those with the C allele (CC/CT) (OR = 2.568, 95% CI: 1.244 - 5.303; p = 0.011). There was no significant association between MTHFR C677T genotypes and HCC stages based on BCLC staging system.

CONCLUSIONS

MTHFR C677T polymorphism with TT genotype could be a factor that increases the risk of HBVrelated HCC in a Chinese population, especially those with HBV infection duration of more than 20 years.

摘要

背景

亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢的关键酶，C677T突变与酶活性降低有关。多项研究表明其在致癌作用和肿瘤生长中具有调节作用。乙型肝炎病毒（HBV）相关的肝细胞癌（HCC）是全球最常见的肝癌之一。因此，本病例对照研究旨在探讨MTHFR C677T基因多态性在中国人群HBV相关HCC发生发展中的作用。

方法

纳入的研究对象包括204例HBV相关HCC患者和211例未患HCC的HBV感染者。通过基于DNA微阵列的检测方法对MTHFR C677T基因多态性进行基因分型。分析MTHFR C677T基因多态性与HBV相关HCC的关系。

结果

HCC组和对照组之间MTHFR C677T的基因型频率存在统计学差异（p = 0.025）。在调整年龄、性别、HBV感染持续时间和HCC家族史后，在不同遗传模型下，TT基因型与中国人群HBV相关HCC风险升高相关（T vs. C，OR = 1.462，95%CI：1.090 - 1.962，p = 0.011；TT vs. CC，OR = 2.151，95%CI：1.143 - 4.049，p = 0.018；TT vs. CC + CT，OR = 1.918，95%CI：1.215 - 3.026，p = 0.005）。当按已知的HBV感染持续时间分层时，HBV感染持续时间超过20年且携带纯合TT基因型的受试者比携带C等位基因（CC/CT）的受试者对HCC更易感（OR = 2.568，95%CI：1.244 - 5.303；p = 0.011）。基于BCLC分期系统，MTHFR C677T基因型与HCC分期之间无显著关联。