Inflammation in prostate carcinogenesis

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Prostate cancer is the most common form of non-skin cancer in men in developed countries. The cause(s) of prostate cancer have not yet been clarified. Although heritable factors are implicated, immigration studies indicate that environmental exposures are also important. Chronic infection and inflammation cause cancer in several organs including the stomach, liver and large intestine. Data from histopathological, molecular histopathological, epidemiological and genetic epidemiological studies show that chronic inflammation might also be important in prostate carcinogenesis. The source of intraprostatic inflammation is often unknown, but might be caused by infection (for example, with sexually transmitted agents), cell injury (owing to exposure to chemical and physical trauma from urine reflux and prostatic calculi formation), hormonal variations and/or exposures, or dietary factors such as charred meats. The resultant epithelial cellular injury might cause a loss of tolerance to normal prostatic antigens, resulting in a self-perpetuating autoimmune reaction. Exposures to infectious agents and dietary carcinogens are postulated to directly injure the prostate epithelium, resulting in the histological lesions known as proliferative inflammatory atrophy (PIA), or proliferative atrophy. These lesions are postulated to be a manifestation of the 'field effect' caused by environmental exposures. Despite a strong genetic component to prostate cancer risk, no highly penetrant hereditary prostate cancer genes have been uncovered to date. Although complex, genetic variation in inflammatory genes is associated with prostate cancer risk. Several challenges remain regarding the inflammation hypothesis in prostate cancer, including the determination of the cause(s) of chronic inflammation in the prostate, an understanding of the cellular and molecular biology of the immune response in the prostate, whether inflammatory cells are truly causative in the process, and the determination of the target cell types within the proposed precursor lesions of prostate cancer. The refinement and application of new epidemiological approaches, including high-throughput genetic epidemiology, improved rodent models of prostate inflammation and cancer, and advances in the application of molecular techniques to histopathological studies should provide insights into the cause of prostate inflammation and its relevance to prostate carcinogenesis.