Environmental exposures, stem cells, and cancer.

An estimated 70-90% of all cancers are linked to exposure to environmental risk factors. In parallel, the number of stem cells in a tissue has been shown to be a strong predictor of risk of developing cancer in that tissue. Tumors themselves are characterized by an acquisition of "stem cell" characteristics, and a growing body of evidence points to tumors themselves being sustained and propagated by a stem cell-like population. Here, we review our understanding of the interplay between environmental exposures, stem cell biology, and cancer. We provide an overview of the role of stem cells in development, tissue homeostasis, and wound repair. We discuss the pathways and mechanisms governing stem cell plasticity and regulation of the stem cell state, and describe experimental methods for assessment of stem cells. We then review the current understanding of how environmental exposures impact stem cell function relevant to carcinogenesis and cancer prevention, with a focus on environmental and occupational exposures to chemical, physical, and biological hazards. We also highlight key areas for future research in this area, including defining whether the biological basis for cancer disparities is related to effects of complex exposure mixtures on stem cell biology.