CYP2E1基因多态性和DNA损伤修复酶表达对肺癌易感性的影响

Effect of CYP2E1 Polymorphism on DNA Stability and Lung Cancer Susceptibility

[目的 ]研究CYP2E1基因型与不同肺组织中切除修复鼠缺陷交叉互补基因 2蛋白 (ERCC2 )、尿嘧啶DNA糖基化酶 (UDG)、细胞增殖核抗原 (PCNA)的表达水平的关系 ,探讨CYP2E1基因多态性对DNA稳定性和肺癌易感性的影响。 [方法 ]通过免疫组织化学和原位杂交方法研究 3种生物标志物在不同肺组织中蛋白质和mRNA的表达水平 ,同时采用PCR -RFLP方法进行CYP2E1分型。 [结果 ]在 3种CYP2E1基因型 (ww、mw、mm)中 ,ww和mm基因型对ERCC2的表达有明显影响 ,mw基因型对UDG的表达有明显影响 ,3种基因型均与PCNA的表达有关。交互分析结果显示CYP2E1多态性与UDG的表达存在交互作用。 [结论 ]不同个体CYP2E1遗传多态性与DNA切除修复功能有关 ,并存在CYP2E1与UDG的交互作用 ,两者在肺癌易感性中均具有一定的作用。

To study the effect of CYP2E1 polymorphism on DNA stability and lung cancer susceptibility through the expression level of ERCC2,UDG,PCNA in different lung tissues. The protein and mRNA expression levels of ERCC2,UDG,PCNA were detected using immunohistochemistry and in situ hybridization in 61 cases of lung cancer, 41 cases of benign lung tissues. CYP2E1 polymorphism was detected by PCR-RFLP. Of the three(ww,mw,mm) CYP2E1RsaI polymorphism, ww and mm genotypes had significant effect on ERCC2 expression, mw genotype had significant effect on UDG expression, and all the three genotypes had effect on PCNA expression. CYP2E1 polymorphism was interacted with UDG expression. [Conclusion] CYP2E1 polymorphism was related to DNA damage repair capability, and interacted with UDG expression. Both CYP2E1 polymorphism and DNA repair enzyme expression may be related with lung cancer susceptibility.