中文摘要：

目的：探讨丝裂原活化蛋白激酶激酶4（mitogen-activated protein kinase kinase4,MKK4）基因启动子区单核苷酸多态性与中国南方人群肺癌发病风险的关系。方法：采用病例对照研究方法,收集800例肺癌病例和900例正常对照,采用TaqMan技术检测MKK4基因启动子区多态位点rs3826392（-1304T〉G）的基因型。应用SAS9.3软件分析其与肺癌易感性的相关性。结果：MKK4基因启动子区-1304T〉G基因型在对照组中的频率分布符合Hardy-Weinberg平衡（P=0.149）,其在病例组和对照组的分布差异有统计学意义（P=0.001）;与携带TT基因型个体相比,携带TG杂合子的个体患肺癌的风险下降25%[校正比值比（oddratio,OR）=0.75,95%可信区间（confidence interval,CI）=0.58～0.97],而携带GG变异纯合子者患肺癌的风险下降45%（校正OR=0.55,95%CI=0.33～0.94）;随着变异型等位基因G的个数增加,肺癌发病风险逐步降低（P趋势〈0.001）。结论：MKK4基因启动子区-1304T〉G基因遗传变异可能降低肺癌发病风险。

英文摘要：

Objective： To investigate the association between the single nucleotide polymorphism （SNP） of mitogen-activated protein kinase kinase 4 （MKK4） promoter and the risk of lung cancer development in Southern Chinese population. Methods： A hospital-based case-control study including 800 cases of lung cancer and 900 healthy controls was conducted. TaqMan assay was used to test the SNP of rs3826392 （-1304T〉G） in MKK4 promoter, and the software SAS 9.13 was used to analyze the association of MKK4 polymorphism and the susceptibility of lung cancer. Results： The observed genotype frequency of -1304T〉 G in MKK4 promoter was appropriate for Hardy-Weinberg equilibrium in the healthy controls （P = 0.149）. The distribution of genotypes was significantly different between the cases of lung cancer and the healthy controls （P=0.001）. Compared with homozygous genotype （TT）, the risk for lung cancer was decreased by 25% in the carriers of heterozygous genotype （TG） [adjusted odd ratio （OR） = 0.75, 95% confidence interval （CI） = 0.58-0.97）], and the risk for lung cancer in carriers of GG homozygote was decreased by 45% （adjusted OR = 0.55, 95% CI = 0.33-0.94）. There was a significantly decreased trend in the risk for lung cancer along with the increased number of mutation-typic G allele （Ptrend〈0.001）. Conclusion： These findings demonstrate that -1304T〉G genotype in promoter region of MKK4 gene may contribute to the decreased risk of lung cancer.