O^6-甲基鸟嘌呤DNA甲基转移酶Leu84Phe位点多态性与肺癌易感性的Meta分析

Meta-analysis of the association between O^6-methylguanine-DNA-methyltransferase Leu84Phe polymorphism and lung cancer susceptibility

目的综合评价O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)基因Leu84Phe(C->T)位点多态性与肺癌易感性的关系。方法检索中国医学文献数据库和PUBMED,得到MGMT基因Leu84Phe位点多态性与肺癌易感性关系的病例和对照研究,采用Meta分析的方法合并Leu84Phe位点多态性与肺癌易感性关系的OR值,然后进行亚组分析、敏感性分析和文献的发表偏倚检验。结果本次Meta分析共纳入6篇文献,累计病例2 513例,对照2 671例。在显性基因模型下,CT+TT基因型对于CC基因型的合并OR值为1.05(95%CI为0.92~1.19),该OR值经Z检验,差异无统计学意义(P>0.05);亚洲人组CT+TT基因型对于CC基因型合并OR值为0.91(95%CI为0.73~1.15),该OR值经Z检验,差异无统计学意义(Z=0.78,P>0.05);欧洲人组CT+TT基因型对于CC基因型合并OR值为1.12(95%CI为0.96~1.31),该OR值经Z检验,差异无统计学意义(Z=1.41,P>0.05)。在隐性基因模型下,CC+CT基因型对于TT基因型合并OR值为0.76(95%CI为0.51~1.12),该OR值经Z检验,差异无统计学意义(Z=1.39,P>0.05);亚洲人组合并OR值为1.43(95%CI为0.61~3.36),该OR值经Z检验,差异无统计学意义(Z=0.82,P>0.05),欧洲人组合并OR值为0.64(95%CI为0.41~0.99),该OR值经Z检验,差异有统计学意义(P<0.05)。在显性模型下对文献进行的敏感性分析显示,Meta分析结果稳定,如果去除任何1篇文献,Meta分析的结果都无明显变化。进一步采用Egger’s检验分析漏斗图的对称性,结果显示t=0.51,P>0.05,无发表偏倚存在。结论 MDMT基因Leu84Phe位点多态性与肺癌易感性无相关性;但在欧洲人中,经隐性模型分析表明该基因位点多态性与肺癌的易感性具有一定的相关性。

Objective To evaluate the association between O6-methylguanine-DNA-methyltransferase （MGMT） Leu84Phe （C-〉T） polymorphism and lung cancer susceptibility. Methods We retrieved China biology medicine （CBM） disc and PUBMED to retrieve the case-control studies on the association between MGMT Leu84Phe polymorphism and lung cancer susceptibility, and pooled the OR of the association between MGMT Leu84Phe polymorphism and lung cancer susceptibility by meta-analysis. Then we performed subgroup analysis, sensitivity analysis and publication bias test. Results Six studies containing 2 513 cases and 2 671 controls were enrolled in this meta-analysis, in dominant model, the pooled OR of CT＋ TT genotype compared to CO genotype was 1.05 without statistically significant association （95%O1= 0.92- 1.19） by Z test （P〉0.05）; the pooled OR was 0.91 （95% CI, 0.73- 1.15, Z=0.78） in Asian subgroup and 1. 12 （95% CI, O. 96- 1.31, Z = 1.41） in Caucasian subgroup （P 〉 0.05）. In recessive model, the pooled OR of CT ＋ CC genotype compared to TT genotype was 0.76 （95% CI： 0.51 - 1.12） without statistically significant association （Z= 1.39, P〉0.05）; the pooled OR in Asian subgroup was 1.43 （95%CI= 0.61-3.36, Z=0.82, P〉0.05）, while the pooled OR was 0.64 in Caucasian subgroup with statistically significant association （95 % OI, 0.41 -- 0.99） by Z test （P〈0.05）. Meta-analysis result was stable to perform sensitivity analysis in dominant model. When any paper was deleted, there was no significant difference in meta-analysis results. Furthermore, we performed the Egger＇s test to analyze the funnel graph symmetry and there was no publication bias （ t = 0.51, P〉0.05）. Conclusion The Leu84Phe polymorphism in MGMT is not correlated with lung cancer susceptibility. However, the TT genotype is a risk factor for lung cancer susceptibility in Caucasian recessive model.