Oxidative DNA damage and DNA repair mediate the development of several human pathologies, including
cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER). Functional assays performed in blood leukocytes of
cancer patients and matched controls show that specific BER pathways are decreased in
cancer patients, and may be risk factors. These include
8-oxoguanine (8-oxoG) repair in lung and
head and neck cancer patients and repair of lipid peroxidation (LPO) induced
1,N(6)-ethenoadenine (epsilonA) in
lung cancer patients. Decrease of excision of LPO-induced DNA damage, epsilonA and
3,N(4)-ethenocytosine (epsilonC) was observed in blood leukocytes of patients developing
lung adenocarcinoma, specific histological type of
cancer related to
inflammation and healing of
scars. BER
proteins activity depends on gene polymorphism, interactions between BER system partners and post-translational modifications. Polymorphisms of
DNA glycosylases may change their enzymatic activities, and some polymorphisms increase the risk of
inflammation-related
cancers, colorectal, lung and other types. Polymorphisms of BER platform
protein, XRCC1 are connected with increased risk of tobacco-related
cancers. BER efficiency may also be changed by
reactive oxygen species and some diet components, which induce transcription of several glycosylases as well as a major human
AP-endonuclease, APE1. BER is also changed in
tumors in comparison to unaffected surrounding tissues, and this change may be due to transcription stimulation, post-translational modification of BER
enzymes as well as
protein-
protein interactions. Modulation of BER
enzymes activities may be, then, an important factor determining the risk of
cancer and also may participate in
cancer development.