Alterations in the levels of oxidative damage in sporadic colorectal cancer

Oxidative DNA damage can be caused by reactive oxygen species (ROS), and 8-oxo-dG is a key biomarker of oxidative DNA damage. The base-excision repair pathway (BER) is the major pathway for repair of oxidative damage, the mis-match repair (MMR) system being an important backup repair pathway. Using tissue microarrays and immunohistochemistry, we examined levels and localization of 8-oxo dG in matched tumour and normal tissues from 47 sporadic colorectal cancers. Loss of mis-match repair proteins, MLH1 and MSH2 was assessed to determine interactions between BER and MMR pathways. Total 8-oxo-dG positivity were significantly elevated in normal mucosa (mean 70.1 [SD 23.9]) compared to tumour (36.9 [38.9]) (p<0.001). Individual levels, both in epithelial and stromal cells were greater in normal than tumour (p<0.001 in each case). Total intensity levels were also significant in each case (p<0.001). There was no association between 8-oxo-dG and loss of mis-match repair proteins in tumours (p=0.7). Increased ROS and inflammation may contribute to the increased levels of 8-oxo-dG in normal tissue with subsequent promotion of genomic instability and consequent risk of cancer development.