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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。
Objective: To investigate the relationship between single nucleotide polymorphisms in the promoter region of mitogen-activated protein kinase kinase 4 (MKK4) gene and the risk of lung cancer in southern Chinese population. Methods: A case-control study was conducted in 800 lung cancer patients and 900 healthy controls. The genotypes of rs3826392 (-1304T> G) polymorphism in the promoter region of MKK4 gene were detected by TaqMan technique. SAS9.3 software was used to analyze its association with lung cancer susceptibility. Results: The frequency distribution of -1304T> G genotype of MKK4 gene in the control group was consistent with Hardy-Weinberg equilibrium (P = 0.149), and there was significant difference in the distribution of MKK4 gene between the case group and the control group (P = 0.001) ; Individuals with TG heterozygotes had a 25% lower risk of developing lung cancer than those carrying the TT genotype (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.58-0.97 ], While the risk of lung cancer was 45% lower in patients with GG homozygotes (adjusted OR = 0.55, 95% CI = 0.33 to 0.94). The incidence of lung cancer was gradually reduced as the number of variant G alleles increased P trend <0.001). Conclusion: The genetic variation of -1304T> G gene in MKK4 gene promoter may reduce the risk of lung cancer.