谷胱甘肽S-转移酶M1和谷胱甘肽S-转移酶T1无效基因型增加肝细胞癌风险：基于46项研究的证据
GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies.
作者信息
Li Shanli, Xue Feng, Zheng Yi, Yang Pengtao, Lin Shuai, Deng Yujiao, Xu Peng, Zhou Linghui, Hao Qian, Zhai Zhen, Wu Ying, Dai Zhijun, Chen Shu
机构信息
Department of Interventional Vascular Surgery, The Affiliated Bao ji Central Hospital of Xi'an Jiaotong University College of Medicine, Bao ji, 721008 Shaan xi China.
2Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 China.
出版信息
Cancer Cell Int. 2019 Mar 29;19:76. doi: 10.1186/s12935-019-0792-3. eCollection 2019.
BACKGROUND
It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione -transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC.
METHODS
We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0).
RESULTS
The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null.
CONCLUSIONS
Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.
背景
众所周知，肝细胞癌（HCC）一直是全球最具生命威胁的疾病之一。大量的内在和外在因素已被证明与HCC相关，如基因突变、病毒性肝炎和亚硝胺。尽管先前的研究表明谷胱甘肽 - 转移酶（GST）基因型与HCC有关，但结论并不一致。因此，我们进行了一项新的荟萃分析，以阐述GSTM1基因缺失、GSTT1基因多态性与HCC风险之间的联系。
方法
我们检索了PubMed、Web of Science、Embase和中国知网数据库，以选择符合纳入标准的合格研究，截至2018年7月31日。最终，我们在这项荟萃分析中选择了41篇文章，共6124例病例和9781例对照。我们使用比值比（OR）和95%置信区间（CI）来评估GSTM1和GSTT1基因缺失与HCC风险之间的关联强度。所有统计过程均由Stata（12.0版）执行。
结果
汇总分析表明，GSTM1基因缺失基因型（OR = 1.37，95% CI = 1.18 - 1.59）和GSTT1基因缺失基因型（OR = 1.43，95% CI = 1.23 - 1.66）均增加了HCC的风险。并且GSTM-GSTT1双基因缺失基因型也增加了HCC的风险（OR = 1.58，95% CI = 1.22 - 2.05）。在亚组分析中，按种族分层时，我们在亚洲人中获得了显著结果，结果为GSTM1基因缺失OR = 1.44，95% CI =（1.22 - 1.71），GSTT1基因缺失OR = 1.48，95% CI =（1.25 - 1.77），GSTM1 - GSTT1基因缺失OR = 1.58，95% CI =（1.19 - 2.09），而在白种人或非洲人中未获得显著结果。对对照类型的分层分析表明，在健康人群中，GSTM1、GSTT1单基因缺失基因型和GSTM1 - GSTT1双基因缺失基因型与HCC风险较高相关。除了GSTT1单基因缺失外，在慢性肝病（CLD）中未发现显著关联的证据。
结论
我们的研究表明，携带GSTM1、GSTT1单基因缺失基因型以及GSTT1 - GSTM1双基因缺失基因型的个体更易发生HCC。
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