Miaomiao Wang1, Haiyan Chu, Shizhi Wang, Meilin Wang, Wei Wang, Suping Han, Zhengdong Zhang. 1. Institute of Toxicology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Abstract
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.
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.
Authors: Jae Sung Park; Hye Lim Kim; Yeo Jin Kim; Jong-Il Weon; Mi-Kyung Sung; Hai Won Chung; Young Rok Seo Journal: Oxid Med Cell Longev Date: 2014-08-26 Impact factor: 6.543