Ye Zheng, Song Honglin, Higgins Julian P T, Pharoah Paul, Danesh John
Department of Public Health and Primary Care, University of Cambridge, Strangeways Site, Cambridge, United Kingdom.
PLoS Med. 2006 Apr;3(4):e91. doi: 10.1371/journal.pmed.0030091. Epub 2006 Mar 7.
Glutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results.
Literature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of five GST polymorphisms (GSTM1 null, GSTT1 null, I105V, and A114V polymorphisms in the GSTP1 genes, and GSTM3 intron 6 polymorphism) available before August, 2005, with investigation of potential sources of heterogeneity. Included in the present meta-analysis were 130 studies, involving a total of 23,452 lung cancer cases and 30,397 controls. In a combined analysis, the relative risks for lung cancer of the GSTM1 null and GSTT1 null polymorphisms were 1.18 (95% confidence interval [CI]: 1.14-1.23) and 1.09 (95% CI: 1.02-1.16), respectively, but in the larger studies they were only 1.04 (95% CI: 0.95-1.14) and 0.99 (95% CI: 0.86-1.11), respectively. In addition to size of study, ethnic background was a significant source of heterogeneity among studies of the GSTM1 null genotype, with possibly weaker associations in studies of individuals of European continental ancestry. Combined analyses of studies of the 105V, 114V, and GSTM3*B variants showed no significant overall associations with lung cancer, yielding per-allele relative risks of 1.04 (95% CI: 0.99-1.09), 1.15 (95% CI: 0.95-1.39), and 1.05 (95% CI: 0.89-1.23), respectively.
The risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies.
已知谷胱甘肽S-转移酶（GSTs）可消除或降低细胞内有助于解毒环境致癌物（如烟草烟雾中的致癌物）的酶的活性。有人提出，GST基因多态性是肺癌的危险因素，但大量研究报告的结果明显相互矛盾。
在2005年8月之前所有关于五种GST多态性（GSTM1缺失、GSTT1缺失、GSTP1基因中的I105V和A114V多态性以及GSTM3内含子6多态性）的相关研究的调查人员提供的表格数据基础上，进行基于文献的荟萃分析，并调查潜在的异质性来源。本荟萃分析纳入了130项研究，共涉及23452例肺癌病例和30397例对照。在综合分析中，GSTM1缺失和GSTT1缺失多态性导致肺癌的相对风险分别为1.18（95%置信区间[CI]：1.14 - 1.23）和1.09（95%CI：1.02 - 1.16），但在规模较大的研究中，它们分别仅为1.04（95%CI：0.95 - 1.14）和0.99（95%CI：0.86 - 1.11）。除了研究规模外，种族背景是GSTM1缺失基因型研究中异质性的一个重要来源，在欧洲大陆血统个体的研究中关联可能较弱。对105V、114V和GSTM3*B变异体的研究进行综合分析显示，与肺癌总体无显著关联，每个等位基因的相对风险分别为1.04（95%CI：0.99 - 1.09）、1.15（95%CI：0.95 - 1.39）和1.05（95%CI：0.89 - 1.23）。
肺癌风险与GSTP1基因中的I105V和A114V多态性或GSTM3内含子6多态性无强烈关联。鉴于在规模较大的研究中无显著关联，GSTM1缺失和GSTT1缺失多态性与肺癌总体呈弱阳性关联的相关性尚不确定。由于肺癌有重要的环境病因，要了解普通人群中基因对肺癌的任何贡献，需要开展特别大规模和全面的研究。
