Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk
Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk
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DOI：
10.1093/carcin/23.8.1343
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发表时间：
2002-08-01
期刊：
影响因子：
4.7
通讯作者：
Taioli, E
中科院分区：
文献类型：
--
作者：
Benhamou, S;Lee, WJ;Taioli, E
肺癌的易感性可能部分归因于烟草致癌物代谢活化或解毒的个体间差异。谷胱甘肽S-转移酶M1（GSTM 1）基因多态性已被广泛研究，在这种情况下，最近的病例对照研究的荟萃分析表明GSTM 1缺失和肺癌之间的关联。在这些综述之后，至少发表了15项研究。我们进行了一项新的荟萃分析，总结了43项已发表的病例对照研究的结果，包括> 18000例患者。发现GSTM 1缺失基因型个体的肺癌风险略高（比值比（OR）= 1.17，95%置信区间（CI）1.07-1.27）。没有发现发表偏倚的证据（P = 0.4），但是，估计这种偏倚的程度并不容易，我们不能排除我们的结果中存在一定程度的发表偏倚。对环境致癌物遗传易感性国际合作研究（GSEC）21项病例对照研究中约9500例受试者的原始数据进行汇总分析，以评估GSTM 1基因型作为吸烟对肺癌风险影响的修饰因子的作用。分析显示，没有证据表明GSTM 1无效基因型携带者肺癌风险增加（年龄、性别和中心调整OR = 1.08，95%CI 0.98-1.18），也没有证据表明GSTM 1基因型与吸烟状况或累积烟草消费量之间存在相互作用。
Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07-1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98-1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.