Health effects of PFASs on five major human cancers: A network toxicology perspective on molecular pathogenesis

Area of Science:

• Environmental Health
• Toxicology
• Cancer Research

Background:

• Growing evidence links per- and polyfluoroalkyl substances (PFASs) to human cancer risks.
• Limited research exists on the specific carcinogenic mechanisms of PFASs.
• Network toxicology and high-throughput sequencing offer novel approaches to study these mechanisms.

Purpose of the Study:

• To analyze the carcinogenic effects and mechanisms of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in five major human cancers.
• To identify common and distinct molecular pathways involved in PFAS-induced carcinogenesis.
• To provide a basis for health assessments and mechanistic verification of PFASs.

Main Methods:

• Network toxicology analysis.
• High-throughput sequencing data analysis.
• Comparative analysis of PFOA and PFOS effects across gastric, colorectal, liver, kidney, and breast cancers.

Main Results:

• PFOS carcinogenesis involved 24 enriched pathways, with Ribosome pathways noted in rectal, liver, and kidney cancers.
• PFOA carcinogenesis involved 32 enriched pathways, notably the peroxisome proliferator-activated receptor (PPAR) signaling pathway in all five cancers.
• PFOA primarily acts through the PPAR pathway, while PFOS disrupts reactive oxygen species and ribosomes.

Conclusions:

• PFOA and PFOS, despite structural similarities, exhibit different carcinogenic mechanisms.
• PFOA-induced cancer is linked to PPAR signaling.
• PFOS-induced cancer is associated with disturbances in reactive oxygen species and ribosome pathways.