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.
Highlights
Colorectal cancer is a major cause of cancer-associated morbidity and mortality worldwide
In view of the role of the polymorphism in base excision repair (BER) enzymes in colorectal carcinogenesis, we evaluated the influence of the APE1 Asp148Glu polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer
We described a role for the BER genes, APE1, XRCC1, PARP1 and OGG1, in colorectal carcinogenesis
Summary
Colorectal cancer is a major cause of cancer-associated morbidity and mortality worldwide. The colon epithelium is one of the most constantly regenerated tissues in the human body and, is more vulnerable to a variety of mutagenic compounds present in the intestine and/or blood Lifestyle choices, such as smoking and the consumption of alcohol, red meat and processed foods high in saturated fat, have been described as risk factors for developing colorectal cancer through the generation of oxidative DNA damage [7]. In view of the role of the polymorphism in BER enzymes in colorectal carcinogenesis, we evaluated the influence of the APE1 Asp148Glu polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. We described a role for the BER genes, APE1, XRCC1, PARP1 and OGG1, in colorectal carcinogenesis
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