Background: Cytochrome P450A1 (CYP1A1) gene and glutathione S-transferase M1 (GSTM1) gene both have single nucleotide polymorphisms and effects on lung cancer. Currently, however, the risk of lung cancer due to the CYP1A1 and GSTM1 genes has no clear evidence. In this present study, we propose to research the combined effects of CYP1A1 gene and GSTM1 gene polymorphism and their risks to lung cancer.
Methods: We conducted the study at different research areas and using various database, including PubMed, Embase, China Biology Medicine (CBM) and China National Knowledge Infrastructure (CNKI) last March 31, 2011. We calculated the adjusted odds ratio (OR) and 95% confidence interval (CI) for lung cancer in each study. Using STATA 10, a statistical program, we summarized the calculated estimates for the adjusted ORs and performed a meta-analysis.
Results: The meta-analysis includes 15 research studies. The CYP1A1 IIe/Val genotype which carries a homozygous mutant type has a higher chance of risk to lung cancer than that which carries a homozygous mutant type and a heterozygous type when the GSTM1 carries a null genotype. As a result, OR was 3.18 (95%CI: 1.27-7.98), 1.45 (95%CI: 1.08-1.94), respectively. Meanwhile, the same conclusion was obtained for the CYP1A1 MspI genotype. The overall OR was 1.90 (95%CI: 1.00-3.58), 1.57 (95%CI: 1.23-2.00), respectively.
Conclusions: We discovered through our meta-analysis that the combined effects of CYP1A1 gene and GSTM1 gene polymorphism are significantly associated with an increased risk to lung cancer. We also found that homozygous mutant genotype of CYP1A1 has a higher chance of risk to lung cancer than the homozygous or heterozygous genotype.
背景与目的: 谷胱甘肽转移酶M1(glutathione S-transferase M1, GSTM1)和细胞色素P4501A1(cytochrome P450A1, CYP1A1)均存在基因多态性，并且对肺癌发病风险有一定的影响，两者联合作用对肺癌发病风险的影响尚无确切定论。本研究旨在探讨CYP1A1和GSTM1基因多态性及其联合效应与肺癌危险性的关系。
方法: 在PubMed数据库、EMBASE数据库、中国生物医学文献数据库(china biology medicine, CBM)和中国知识基础设施工程数据库(china national knowledge infrastructure, CNKI)中查询文献，时间范围从各数据库建库至2011年3月。使用STATA 10软件进行meta分析统计，对于每篇入选的文献均计算肺癌发生危险性调整混杂因素后优势比(odd ratio, OR)及其95%置信区间(confidence interval, CI)。
结果: 15篇文献最终被纳入本次研究。Meta分析显示GSTM1基因缺失时CYP1A1基因IIe/Val位点为纯合突变型时肺癌发病风险明显高于杂合型与纯合突变型联合，总体OR分别为3.18(95%CI: 1.27-7.98)和1.45(95%CI: 1.08-1.94)。GSTM1基因缺失时CYP1A1基因MspI位点为纯合突变型时肺癌发病风险也高于杂合型与纯合突变型联合，总体OR分别为1.90(95%CI: 1.00-3.58)和1.57(95%CI: 1.23-2.00)。
结论: CYP1A1和GSTM1基因多态性联合作用增加了单个基因多态性发生肺癌的危险性。CYP1A1纯合突变型基因对人群肺癌易感性的影响明显大于野生型和杂合突变型。