Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

Biomedical Centre Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 323 00 Pilsen Czech Republic

Department of Biology Faculty of Education J Selye University Bratislavska 3322 945 01 Komarno Slovakia

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

Department of Surgery University Hospital Kralovske Vinohrady Prague 3rd Medical Faculty Charles University Ruska 87 100 00 Prague Czech Republic

Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences University of Defence Trebesska 1575 500 01 Hradec Kralove Czech Republic

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Albertov 4 128 00 Prague Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

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