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

• Grant number: 14/20517-0
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: November 01, 2014
• End date: April 30, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcelo Lima Ribeiro
• Grantee: Marcelo Lima Ribeiro
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

It has been hypothesised 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 tumour samples from patients with colorectal cancer. The results indicate a down-regulation of OGG1 and an up-regulation of XRCC1 expression in tumour 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 tumour invasion, a significant down-regulation in OGG1 was observed in tumour tissue. Interestingly, when taking into account the tumour 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 tumour 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 (AU)