Genetic variant in APE1 gene promoter contributes to cervical cancer risk
Genetic variant in APE1 gene promoter contributes to cervical cancer risk
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DOI：
10.1016/j.ajog.2013.07.010
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发表时间：
2013-10-01
影响因子：
9.8
通讯作者：
Zhang, Zhengdong
中科院分区：
文献类型：
--
作者：
Wang, Miaomiao;Chu, Haiyan;Zhang, Zhengdong
目的：脱嘌呤/脱嘧啶核酸内切酶1（Apurinic/apyrimidinic endonuclease 1，APE 1）是碱基切除修复途径中的必需酶，在DNA氧化和烷基化损伤的修复中起重要作用。然而，APE 1与宫颈癌风险相关的确切机制仍不清楚。本研究探讨APE 1 - 656 T>G多态性是否与宫颈癌风险有关。研究设计：在以医院为基础的病例对照研究中，采用聚合酶链反应限制性片段长度多态性方法对306例宫颈癌病例和306名无癌对照进行APE 1 - 656 T>G多态性基因分型。结果：多因素Logistic回归分析显示，APE 1 - 656 TG/GG基因型个体与TT基因型个体相比，发生宫颈癌的风险显著降低（调整后的比值比，0.61; 95%置信区间，0.42-0.89）。3株细胞的荧光素酶检测结果显示，APE 1 - 656 T>G置换可增加APE 1的表达，这与相关性研究的结果一致。结论：APE 1 - 656 T> G多态性可能通过影响转录因子与启动子的结合亲和力，导致APE 1表达水平升高，从而与中国人群宫颈癌的发病风险相关。
OBJECTIVE: Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway, which plays an important role in repairing DNA damage caused by oxidation and alkylation. However, the exact mechanism of APE1 associated with cervical cancer risk is still unknown. In this study, we explored whether the APE1 -656T>G polymorphism contributed to the risk of cervical cancer.STUDY DESIGN: In the hospital-based case-control study, 306 cervical cancer cases and 306 cancer-free controls were genotyped for the APE1 -656T>G polymorphism using the polymerase chain reaction restriction fragment length polymorphism method. Luciferase reporter assay and electrophoretic mobility shift assay were used to evaluate the APE1 transcriptional activity and the binding ability of transcriptional factors to the APE1 promoter, respectively.RESULTS: Logistic regression analysis showed that individuals with the APE1 -656 TG/GG genotypes had a significantly reduced risk of cervical cancer compared with the TT genotype (adjusted odds ratio, 0.61; 95% confidence interval, 0.42-0.89). The luciferase assays in 3 cell lines showed that the APE1 -656T>G substitution can increase the expression of APE1, which was consistent with the finding of association study. Electrophoretic mobility shift assay further indicated that the APE1 -656T>G polymorphism enhanced the binding affinity of transcriptional factors to the promoter region.CONCLUSION: These findings suggested that the APE1 -656T>G polymorphism was associated with cervical cancer risk in a Chinese population by affecting the binding affinity of transcriptional factors to the promoter, leading to an increased expression level of APE1.