Effect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer

• Published in: International journal of molecular sciences 2014-09, Vol.15 (10), p.17333-17343
• Main Authors: Santos, Juliana C, Funck, Alexandre, Silva-Fernandes, Isabelle J L, Rabenhorst, Silvia H B, Martinez, Carlos A R, Ribeiro, Marcelo L
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Alleles; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Down-Regulation; Female; Gene expression; Genotype; Genotype & phenotype; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Polymorphism; Polymorphism, Single Nucleotide; Up-Regulation; X-ray Repair Cross Complementing Protein 1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms151017333

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.