剪接蛋白U2AF65基因多态性和吸烟交互作用与胰腺癌风险的关联  

Association between pancreatic cancer risk and the interaction of U2AF65 gene polymorphisms and smoking

作　　者：田晶[1] 朱贝贝[2] 田瑶[1] 钟荣[2] 缪小平[2] 王丽[1] 

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院流行病学和卫生统计学系,北京100005 [2]华中科技大学同济医学院公共卫生学院流行病和卫生统计学系

出　　处：《中华流行病学杂志》2014年第6期710-713,共4页Chinese Journal of Epidemiology

基　　金：国家自然科学基金（81041079）

摘　　要：目的：探讨U2小核糖核蛋白体辅助分子U2AF35和U2AF65功能基因多态性及其与吸烟交互作用与胰腺癌风险关联。方法采用两阶段病例对照研究，筛查阶段采用Openarray中通量分型技术对筛选出的U2AF35和U2AF65基因4个潜在功能标签单核苷酸多态性（SNP）位点在研究对象（武汉地区298例原发胰腺癌病例和525例非肿瘤对照）中进行基因分型；对筛查阶段的阳性位点进一步在验证人群（北京地区413例原发胰腺癌病例和557例非肿瘤对照人群）中采用TaqMan基因分型技术进行验证。并采用加法交互模型分析基因和吸烟交互作用对胰腺癌发生风险的影响。结果筛查阶段U2AF65基因的rs310441和rs310445与胰腺癌发病风险均存在显著关联。对rs310445进行验证后发现，以携带TT基因型者为参照，携带C等位基因者的胰腺癌发病风险增加，合并两阶段人群的OR值为1.31（95%CI：1.07～1.60，P＝0.010）。合并人群观察到吸烟和rs310445 C等位基因之间的协同作用可增加胰腺癌的发生风险，协同指数为2.08（95%CI：1.37～2.78）。未发现U2AF35位点多态与胰腺癌发生风险相关。结论 U2AF65 rs310445 C等位基因与吸烟协同作用可能增加胰腺癌发生风险，但仍需大样本研究验证。Objective To determine the association between U2 small nuclear ribonucleoprotein auxiliary factor 35/65（U2AF35 and U2AF65）and pancreatic cancer（PC）. Methods A two-stage analysis case-control study was conducted. Four candidate tag single nucleotide polymorphisms （tagSNPs）were genotyped by Taqman Openarray assay in a screening population living in Central China（298 PC cases and 525 controls）. Thereafter,rs310445 in U2AF65 was genotyped by TaqMan real-time polymerase chain reaction（RT-PCR）in a validation Chinese Han population from Beijing （413 cases and 557 controls）. Results rs310445 in U2AF65 gene was significantly associated with PC in both screened population and combined population. Subjects with C allele had a higher risk of PC compared to those with the TT genotype,with OR of 1.31（95%CI：1.07-1.60,P=0.010）for the combined population. A synergic effect of smoking and C allele of rs310445 was also observed in the combined population,with Synergic Index of 2.08（95%CI：1.37-2.78） in the combined population. Conclusion Our findings suggested the interaction between smoking and U2AF65 might play a role in PC. These findings should be confirmed by further independently large-scale population studies.

关 键 词：吸烟 胰腺癌 U2小核糖核蛋白体辅助分子 单核苷酸多态性 

分 类 号：R735.9[医药卫生—肿瘤]