中国人群中两种重要的谷胱甘肽S-转移酶基因多态性与肺癌风险的关联：来自71项研究的证据。
The associations between two vital GSTs genetic polymorphisms and lung cancer risk in the Chinese population: evidence from 71 studies.
作者信息
Liu Kui, Lin Xialu, Zhou Qi, Ma Ting, Han Liyuan, Mao Guochuan, Chen Jian, Yue Xia, Wang Huiqin, Zhang Lu, Jin Guixiu, Jiang Jianmin, Zhao Jinshun, Zou Baobo
机构信息
Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China; Department of Science Research and Information Management,Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People's Republic of China.
Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
出版信息
PLoS One. 2014 Jul 18;9(7):e102372. doi: 10.1371/journal.pone.0102372. eCollection 2014.
BACKGROUND
The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population.
METHODS
Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests.
RESULTS
71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004).
CONCLUSIONS
An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.
背景
谷胱甘肽S-转移酶（GSTs）的基因多态性被怀疑与肺癌的发生有关，但目前的研究结果相互矛盾，尤其是在中国人群中。
方法
对来自68项关于谷胱甘肽S-转移酶Mu 1（GSTM1）、17项关于谷胱甘肽S-转移酶theta 1（GSTT1）以及8项关于GSTM1-GSTT1基因多态性的中国人群研究数据重新分析其与肺癌风险的关联。使用森林图汇总比值比（OR）。在亚组分析中对9个亚组全部或部分进行了分析。使用Galbraith图识别异质性记录。通过Begg检验和Egger检验检测潜在的发表偏倚。
结果
在筛选1608篇文章后，确定了71项符合条件的研究。基于可比的异质性，通过随机效应模型检测到两种重要的GSTs基因多态性与肺癌风险之间的关联增加。亚组分析显示，鳞状细胞癌（SC）、腺癌（AC）或小细胞肺癌（SCLC）与GSTM1无效基因型之间存在显著关系，以及SC或AC与GSTT1无效基因型之间存在显著关系。此外，具有GSTM1无效基因型的吸烟者患肺癌的风险高于非吸烟者。我们的累积荟萃分析证明了GSTM1无效基因型与肺癌风险之间关系的稳定可靠结果。在省略可能存在异质性的文章后，GSTs与肺癌易感性的调整后风险增加（固定效应模型：ORGSTM1 = 1.23，95%CI：1.19至1.27，P<0.001；ORGSTT1 = 1.18，95%CI：1.10至1.26，P<0.001；ORGSTM1-GSTT1 = 1.33，95%CI：1.10至1.61，P = 0.004）。
结论
在中国人群中发现，GSTM1和GSTT1无效基因型，尤其是双重无效基因型，会增加患肺癌的风险。此外，未来研究应考虑肺癌的特殊组织病理学分类以及广泛的基因-环境和基因-基因相互作用分析。
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