Involvement of per- and polyfluoroalkyl compounds in tumor development.

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic persistent chemicals, which are used in many industrial and commercial applications. Hundreds of different PFAS have been identified in the environment and they are commonly found also in human blood. Due to the chemical stability and extensive use, PFAS pose a risk for human health and wildlife. Mounting evidence indicates that PFAS-exposure adversely affects many organs including liver, kidney, and reproductive tissues and induces tumors in laboratory rodents. Epidemiological studies show association between PFAS-exposure and some tumors also in humans. Effects of PFAS-exposure are complex and obviously do not depend only on the concentration and the structure of PFAS, but also on age and sex of the exposed individuals. It has been difficult to show a causal link between PFAS-exposure and tumors. Moreover, molecular mechanisms of the PFAS effects in different tissues are poorly understood. PFAS are not directly mutagenic and they do not induce formation of DNA binding metabolites, and thus are assumed to act more through non-genotoxic mechanisms. In this review, we discuss the involvement of PFAS-compounds in tumor development in tissues where PFAS exposure has been associated with cancer in epidemiological and animal studies (liver, kidney, testicle and breast). We will focus on molecular pathways and mechanisms related to tumor formation following PFAS-exposure.