Effect of APE1 T2197G (Asp148Glu) Polymorphism on APE1, XRCC1, PARP1 and OGG1 Expression in Patients with Colorectal Cancer |
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| Authors: | Juliana C Santos Alexandre Funck Isabelle J L Silva-Fernandes Silvia H B Rabenhorst Carlos A R Martinez Marcelo L Ribeiro |
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| Affiliation: | 1.Laboratory of Microbiology and Molecular Biology, Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Bragança Paulista, SP. 12916-900, Brazil; E-Mails: (J.C.S.); (A.F.); (C.A.R.M.);2.Genetics and Molecular Biology, UNICAMP, Universidade Estadual de Campinas, Campinas, SP. 13083-862, Brazil;3.Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, CE. 60020-181, Brazil; E-Mails: (I.J.L.S.-F.); (S.H.B.R.) |
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| Abstract: | It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis. |
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| Keywords: | colorectal cancer DNA repair APE1 polymorphism BER |
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