Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer
1
Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, Urbana, IL 61802, USA
2
Department of Bioengineering, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA
3
Departments of Urology, Pathology and Physiology, College of Medicine, Chicago Center for Health and Environment, University of Illinois Chicago, Chicago, IL 60612, USA
4
Department of Food Science and Human Nutrition, Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA
5
Institute of Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA
6
Beckman Institute of Technology, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA
7
Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Birandra K. Sinha
Cancers 2022, 14(12), 2919; https://doi.org/10.3390/cancers14122919
Received: 8 May 2022
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Revised: 6 June 2022
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Accepted: 6 June 2022
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Published: 14 June 2022
Simple Summary
Poly- and perfluoroalkylated substances (PFAS) are industrial chemicals found in many household products that persist in the environment. While several excellent review articles exist on the potential harmful effects of PFAS, there are few focused on cancer. This concise and streamlined mini-review focuses on summarizing molecular mechanisms related to the potential cancer-promoting properties of PFAS. This review organizes and interprets the vast primary PFAS cancer biology literature and provides a coherent, unified, and digestible model of the molecular mechanisms that potentially explains PFAS cancer promotion.
Poly- and perfluoroalkylated substances (PFAS) are chemicals that persist and bioaccumulate in the environment and are found in nearly all human populations through several routes of exposure. Human occupational and community exposure to PFAS has been associated with several cancers, including cancers of the kidney, testis, prostate, and liver. While evidence suggests that PFAS are not directly mutagenic, many diverse mechanisms of carcinogenicity have been proposed. In this mini-review, we organize these mechanisms into three major proposed pathways of PFAS action—metabolism, endocrine disruption, and epigenetic perturbation—and discuss how these distinct but interdependent pathways may explain many of the proposed pro-carcinogenic effects of the PFAS class of environmental contaminants. Notably, each of the pathways is predicted to be highly sensitive to the dose and window of exposure which may, in part, explain the variable epidemiologic and experimental evidence linking PFAS and cancer. We highlight testicular and prostate cancer as models to validate this concept.
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Keywords:
PFOA; PFOS; testicular cancer; prostate cancer; epigenetics; metabolomic
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Boyd, R.I.; Ahmad, S.; Singh, R.; Fazal, Z.; Prins, G.S.; Madak Erdogan, Z.; Irudayaraj, J.; Spinella, M.J. Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer. Cancers 2022, 14, 2919. https://doi.org/10.3390/cancers14122919
AMA Style
Boyd RI, Ahmad S, Singh R, Fazal Z, Prins GS, Madak Erdogan Z, Irudayaraj J, Spinella MJ. Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer. Cancers. 2022; 14(12):2919. https://doi.org/10.3390/cancers14122919
Chicago/Turabian StyleBoyd, Raya I., Saeed Ahmad, Ratnakar Singh, Zeeshan Fazal, Gail S. Prins, Zeynep Madak Erdogan, Joseph Irudayaraj, and Michael J. Spinella. 2022. "Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer" Cancers 14, no. 12: 2919. https://doi.org/10.3390/cancers14122919
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