Approximately 20% to 30% of the world’s cancer burden can be traced to infectious agents that are thought to act through the production of chronic infections and subsequent chronic inflammation. For example, adenocarcinoma of the stomach is characterized by a series of sequential events comprising Heliobacter pylori infection, resultant long- standing persistent inflammation, atrophic gastritis, dysplasia, and carcinoma.The molecular mechanisms of inflammation-induced cancer relate to the action of phagocytic inflammatory cells (neutrophils and macrophages) that release a variety of chemical agents designed to kill pathogens. These agents include superoxide, hydrogen peroxide, singlet oxygen, and nitric oxide, which can further react to form the highly reactive peroxynitrite. Some of these reactive oxygen and nitrogen species can directly interact with DNA in host bystander cells or react with other epithelial cellular components, such as phospholipids, initiating a free radical chain reaction – the end result being cell injury and cell death. Lost epithelial cells must regenerate quickly by DNA replication and cell division in order to maintain their barrier function.
This increased DNA synthesis, which is also stimulated locally via cytokines released from inflammatory cells, places epithelial cells at high risk for acquiring oxidative/nitrosative DNA damage and subsequent mutations.
Evidence Suggesting a Link Between Inflammation and Prostate Cancer
A growing body of work from studies of families with hereditary prostate cancer, as well as data from the fields of genetic epidemiology, histopathology, and molecular pathology, has begun to suggest that a link may exist between chronic inflammation and prostate cancer. For instance, case-control epidemiological studies have found an increased relative risk of prostate cancer in men with a prior history of certain sexually transmitted infections (STIs) or prostatitis. Furthermore, genetic epidemiological data have implicated germline variants of several genes directly involved in the response to infection (e.g. RNAseL or macrophage scavenger receptor 1 (MSR1)) in modulating prostate cancer risk.