CAJ | 학술논문

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。
목적：탐토U2소핵당핵단백체보조분자U2AF35화U2AF65공능기인다태성급기여흡연교호작용여이선암풍험관련。방법채용량계단병례대조연구，사사계단채용Openarray중통량분형기술대사선출적U2AF35화U2AF65기인4개잠재공능표첨단핵감산다태성（SNP）위점재연구대상（무한지구298례원발이선암병례화525례비종류대조）중진행기인분형；대사사계단적양성위점진일보재험증인군（북경지구413례원발이선암병례화557례비종류대조인군）중채용TaqMan기인분형기술진행험증。병채용가법교호모형분석기인화흡연교호작용대이선암발생풍험적영향。결과사사계단U2AF65기인적rs310441화rs310445여이선암발병풍험균존재현저관련。대rs310445진행험증후발현，이휴대TT기인형자위삼조，휴대C등위기인자적이선암발병풍험증가，합병량계단인군적OR치위1.31（95%CI：1.07～1.60，P＝0.010）。합병인군관찰도흡연화rs310445 C등위기인지간적협동작용가증가이선암적발생풍험，협동지수위2.08（95%CI：1.37～2.78）。미발현U2AF35위점다태여이선암발생풍험상관。결론 U2AF65 rs310445 C등위기인여흡연협동작용가능증가이선암발생풍험，단잉수대양본연구험증。
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.