EB病毒-MKK4基因遗传变异的交互作用与鼻咽癌危险性研究

Interaction of EB virus-MKK4 SNP and the risk of nasopharyngeal carcinoma

目的:研究EB病毒感染与MKK4基因遗传变异的交互作用在鼻咽癌发病中的作用。方法:收集鼻咽癌病例和正常对照各500名,采用TAQMAN技术分析MKK4基因遗传变异-1304T>G与鼻咽癌发病的关联;并分析基因位点与EB病毒感染状态在鼻咽癌发生中的交互作用。结果:相对TT基因型携带者,G变异基因型鼻咽癌的发病风险下降(TG基因型adjustedOR=0.78,95%CI=0.61～0.94,P=0.02;GG基因型adjustedOR=0.64;95%CI=0.39～0.99;P=0.04),且存在显著的等位基因剂量—效应关联(Ptrend=0.02)。进一步交互作用分析发现EB病毒感染状态可改变G变异基因型降低鼻咽癌发病风险的作用(adjustedP交互作用=0.04)。结论:MKK4基因遗传变异可降低鼻咽癌的发病风险,但其对鼻咽癌的保护作用受EB病毒感染状态影响,提示EB病毒-MKK4基因交互作用可能是我国南方人群易患鼻咽癌的一个危险因素。

Objective To investigate interaction of EBV with MKK4 SNP in the carcinogensis of Nasopharyngeal carcinoma （NPC）. Methods The association between MKK4 SNP-1304 T 〉 G and NPC risk was analyzed in 500 NPC cases and 500 cancer-free controls using TAQMAN technique, and the interaction of gene loci with EB virus infection in nasopharyngeal carcinoma also studied. Results Compared The possible interaction between this SNP and selected variables on cancer risk were with the TY genotype, the association of G variant genotypes and the decreased risk of NPC was statistically significant （adjusted OR = 0.78, 95% CI = 0.61 - 0.94, P = 0.02 for TG; adjusted OR = 0.64, 95% CI = 0.39-0.99, P = 0.04 for GG）. There was a significant trend for an allele dose effect on risk of NPC （Ptrend = 0.02）. Further interaction analysis showed that the G variant genotypes interacted with EBV negative status on reducing cancer risk （Pinteration = 0.04）. Conclusion Our data suggest that MKK4 genetic variation may reduce the risk of nasopharyngeal carcinoma , and the protective role of genetic variant MKK4-1304 T 〉 G is restrained in NPC with EBV infection. These findings implicate the role of EBV-MKK4 interaction as a causative factor for the NPC in southern chinese population.