The inflammatory microenvironment and microbiome in prostate cancer development

Key Points Chronic inflammation is prevalent in the adult prostate and probably has a role in the formation of lesions that are putative risk factors for prostate cancer development Prostatic inflammation might drive prostate carcinogenesis via oxidative stress and the generation of reactive oxygen species that induce mutagenesis or by causing epigenetic alterations that promote neoplastic transformation Prostatic infection might drive an inflammatory prostate microenvironment, and the discovery of a urinary microbiome is probably important in terms of exposure of the prostate to potentially pathogenic microorganisms Epithelial barrier disruption and inflammation in the prostate, once started, could establish a feed-forward mechanism resulting in a chronic, persistent inflammatory state Full characterization of the link between the urinary microbiome and chronic prostatic inflammation might be critical to enable the development of strategies for prostate cancer prevention Sfanos et al . discuss the potentially procarcinogenic role of prostatic infections and inflammation in prostate pathogenesis. They summarize findings that suggest that an aberrant microbiome together with an inflammatory microenvironment are involved in the initiation of prostate cancer precursor lesions. Chronic inflammation promotes the development of several types of solid cancers and might contribute to prostate carcinogenesis. This hypothesis partly originates in the frequent observation of inflammatory cells in the prostate microenvironment of adult men. Inflammation is associated with putative prostate cancer precursor lesions, termed proliferative inflammatory atrophy. Inflammation might drive prostate carcinogenesis via oxidative stress and generation of reactive oxygen species that induce mutagenesis. Additionally, inflammatory stress might cause epigenetic alterations that promote neoplastic transformation. Proliferative inflammatory atrophy is enriched for proliferative luminal epithelial cells of intermediate phenotype that might be prone to genomic alterations leading to prostatic intraepithelial neoplasia and prostate cancer. Studies in animals suggest that inflammatory changes in the prostate microenvironment contribute to reprogramming of prostate epithelial cells, a possible step in tumour initiation. Prostatic infection, concurrent with epithelial barrier disruption, might be a key driver of an inflammatory microenvironment; the discovery of a urinary microbiome indica