DNA修复基因和EB病毒的交互作用与鼻咽癌易感性初步研究

【目的】探讨在鼻咽癌群体中DNA修复基因与EB病毒的交互作用。【方法】选取广东地区以广东话为主要语言的人群建立匹配的鼻咽癌病例和健康对照（病例/对照=755/755），收集其临床流行病学资料、采集外周血样并进行EB病毒抗体检测和SNP基因型分型。利用决策森林方法，分析DNA修复通路104个基因中768个SNP位点和EB病毒在鼻咽癌中的交互作用。【结果】MDC1、ATM、GTF2H4、MLH1、RAD51L1、XPC、GTF2H1与EB病毒的交互作用达到Bonferroni多重检验校正的显著性水准（0.05）。P 值分别为7.62×10-5 、8.20×10-5、8.55×10-5、1.60×10-4、1.80×10-4、2.20×10-4、和2.42×10-4；其鼻咽癌患病风险比OR (95%CI)分别为15.97(4.17-61.11)、11.32(7.22-25.45)、15.94(4.17-64.01)、5.38(4.88-6.74)、151.47(53.79-380.39)、40.92(15.09-112.67)和142.38(53.38-377.5)。进一步生物信息学基因网络分析表明，这些基因可能通过影响EB病毒DNA复制过程等多种直接或间接的方式，改变广东人群鼻咽癌的易感性。【结论】EB病毒与修复基因的交互作用可能是鼻咽癌的另一重要的易感性机制。

Interactions between DNA-repair Genes and Epstein-Barr Virus Associated with the Susceptibility of Nasopharyngeal Carcinoma: A Primary Study

【Objective】To explore the interactions between DNA-repair genes and EBV in nasopharyngeal carcinoma. 【Method】 A matched case and control design (case/control=755/755) was constructed for the population who were mainly speaking Cantonese in Guangdong Province. Clinical epidemiological data were collected, and their peripheral blood samples were subjected to EBV antibody test and SNP genotyping. Analysis of interactions between DNA-repair genes (168 tagging SNPs located in 104 genes involved in DNA repair pathways) and EBV was implemented by using the ensemble decision forest method. 【Results】 The interactions between MDC1, ATM,GTF2H4, MLH1, RAD51L1, XPC, GTF2H1, and EBV were statistically significant after Bonferroni adjustment, with P values of 7.62×10-5, 8.20×10-5, 8.55×10-5, 1.60×10-5, 1.80×10-4, 2.20×10-4, and 2.42×10-4, respectively. Their OR (95%CI) values were 15.97 (4.17-61.11), 11.32 (7.22-25.45), 15.94 (4.17-64.01), 5.38 (4.88-6.74), 151.47 (53.79-380.39), 40.92 (15.09-112.67) and 142.38 (53.38-377.5), respectively. Further bioinformatics gene network analysis revealed that these genes might modify predisposition to nasopharyngeal carcinoma in the Guangdong population via imposing an impact on the DNA replication of EBV or in other ways that are direct or indirect. 【Conclusion】The interactions between DNA repair genes and EBV might be another important mechanism for the susceptibility to nasopharyngeal carcinoma.