Impact of the Ser326Cys polymorphism of the OGG1 gene on the level of oxidative DNA damage in patients with colorectal cancer.

ABSTRACT

As a result of reactive oxygen species operation, cell damage occurs in both cellular organelles and molecules, including DNA. Oxidative damage within the genetic material can lead to accumulation of mutations and consequently to cancer transformation. OGG1 glycosylase, a component of the Base Excision Repair (BER) system, is one of the enzymes that prevents excessive accumulation of 8-oxoguanine (8-oxG), the most common compound formed by oxidative DNA damage. In case of structural changes of OGG1 resulting from polymorphic variants, we can observe a significant increase in the concentration of 8-oxG. Linking individual polymorphisms to DNA repair systems with increased risk of colorectal cancer will allow patients to be classified as high risk and included in a prophylactic program. The aim of the study was to determine the level of oxidative DNA damage and to analyze the distribution of Ser326Cys polymorphism of the OGG1 gene in a group of patients with colorectal cancer and in a control group in the Polish population. MATERIAL AND METHODOLOGY: DNA was isolated from the blood of 174 patients with colorectal cancer. The control group consisted of 176 healthy individuals. The level of oxidative damage was determined by analyzing the amount of 8-oxguanine using the HT 8-oxo-dG ELISA II Kit. Genotyping was performed via the TaqMan method. RESULTS: The obtained results indicate that Ser326Cys polymorphism of the OGG1 gene increases the risk of RJG and is associated with significantly increased levels of 8-oxoguanine. CONCLUSIONS: Based on the results obtained, we conclude that Ser326Cys polymorphism of the OGG1 gene may modulate the risk of colorectal cancer by increasing the level of oxidative DNA damage.