Cancer Development and Progression Through a Vicious Cycle of DNA Damage and Inflammation

Infections and chronic inflammation play a crucial role in the development of cancer. During inflammatory processes, reactive oxygen and nitrogen species are generated by both inflammatory and epithelial cells, leading to the induction of oxidative and nitrative DNA damage, such as the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine (8-nitroG). These DNA alterations can trigger mutations, which are believed to contribute to cancer formation driven by inflammation. The authors observed the generation of 8-nitroG through iNOS expression in human and animal tissues under inflammatory conditions, where cancer is likely to develop. 8-NitroG serves as a predictive and prognostic indicator for cancers linked to inflammation. Inflammation causes DNA damage, and the subsequent DNA damage response can create an inflammatory environment marked by hypoxia, with HMGB1 being a key factor. The interplay between HIF-1α, NF-ĸB, and HMGB1 sustains DNA damage and the accumulation of mutations, driving cancer progression and worsening prognosis. 8-NitroG is involved not only in the onset and advancement of cancer but also in its progression and conversion. Herein, the authors propose a vicious cycle of DNA damage and inflammation in cancer development (initiation and promotion) and progression, including conversion, via HMGB1.