Li Wen, Song Li-Qiang, Tan Jian
Department of Thoracic Surgery, General Hospital of Beijing Military Command, 5 Nan Men Cang Road, Dong Si Shi Tiao Street, Beijing, 100700, China,
Tumour Biol. 2014 Sep;35(9):9281-90. doi: 10.1007/s13277-014-2212-6. Epub 2014 Jun 18.
Genetic polymorphisms of cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes might contribute to the variability in individual susceptibility to lung cancer, but the reported results from individual studies are not always consistent. We therefore conducted a meta-analysis to systematically estimate the associations between polymorphisms of these two genes and risk of lung cancer. Twenty-one studies with 8,926 subjects were finally enrolled into this study. Meta-analysis was performed by RevMan 5.2. Odds ratio (OR) and its 95 % confidence interval (CI) were calculated to evaluate the susceptibility to lung cancer. Compared with the wild-type homozygous genotype, significantly elevated risk of lung cancer were associated with variant CYP1A1 MspI (m1/m2 + m2/m2 vs. m1/m1: OR = 1.27, 95 % CI = 1.12-1.43, P < 0.001) and deletion of GSTM1 (null vs. present: OR = 1.26, 95 % CI = 1.13-1.40, P < 0.001). Both the two genetic polymorphisms were independently associated with the risk of lung cancer. The pooled OR of lung cancer for population with both CYP1A1 MspI and GSTM1 mutations (MspI m1/m2 or m2/m2 and GSTM1 null) was 1.62 (95 % CI 1.27-2.07, P < 0.001) when compared with those without any of the above mutations, which is higher than single genetic polymorphism. In the stratified analysis, significantly higher risks of lung cancer associated with above genetic polymorphisms were found only in Asian population. This meta-analysis suggests that the CYP1A1 MspI and GSTM1 polymorphisms correlate with increased lung cancer susceptibility independently, and that there is an interaction between the two genes. However, the associations vary in different ethnic populations.
细胞色素P450 1A1（CYP1A1）和谷胱甘肽S-转移酶M1（GSTM1）基因的遗传多态性可能导致个体对肺癌易感性的差异，但个别研究报告的结果并不总是一致。因此，我们进行了一项荟萃分析，以系统评估这两个基因的多态性与肺癌风险之间的关联。最终，本研究纳入了21项研究，共8926名受试者。使用RevMan 5.2进行荟萃分析。计算比值比（OR）及其95%置信区间（CI）来评估对肺癌的易感性。与野生型纯合基因型相比，CYP1A1 MspI变异型（m1/m2 + m2/m2与m1/m1相比：OR = 1.27，95%CI = 1.12 - 1.43，P < 0.001）和GSTM1缺失（无效型与存在型相比：OR = 1.26，95%CI = 1.13 - 1.40，P < 0.001）与肺癌风险显著升高相关。这两种基因多态性均与肺癌风险独立相关。与没有上述任何一种突变的人群相比，同时具有CYP1A1 MspI和GSTM1突变（MspI m1/m2或m2/m2且GSTM1无效）的人群患肺癌的合并OR为1.62（95%CI 1.27 - 2.07，P < 0.001），高于单一基因多态性。在分层分析中，仅在亚洲人群中发现上述基因多态性与较高的肺癌风险相关。这项荟萃分析表明，CYP1A1 MspI和GSTM1多态性分别与肺癌易感性增加相关，且这两个基因之间存在相互作用。然而，不同种族人群中的关联有所不同。
