Abstract
BACKGROUND AND AIMS: Per- and poly-fluoroalkyl substances (PFAS) are persistent chemicals that contaminate air, water, soil, and food. Due to their widespread use, PFAS are detectable in most of the US population, raising concerns about potential health impacts, including a possible association with colorectal cancer (CRC). We conducted a scoping review of previously published studies to consolidate the current understanding of PFAS and its effect on CRC risk, identify knowledge gaps, and propose future directions for research. METHODS: We systematically searched PubMed, Scopus, and Web of Science for studies published through December 2024 that examined PFAS exposure in relation to CRC risk or progression. Data were independently extracted using a standardized protocol and structured according to a predefined Population, Exposure, Comparator, Outcome (PECO) framework. To evaluate internal validity, studies were categorized by evidence stream (in vitro, animal, and epidemiological) and assessed using established quality appraisal criteria. RESULTS: Twenty-six studies were identified, including 5 reviews, 3 in vitro studies, 6 animal studies, and 12 epidemiological studies. In vitro research consistently demonstrates that PFAS exposure promotes CRC cell proliferation and migration, highlighting key mechanistic pathways. However, findings from animal and epidemiological studies are mixed, with some indicating increased intestinal tumorigenesis while others report null or protective effects. Notably, major studies were cross-sectional, retrospective, or ecological, emphasizing the need for high-quality longitudinal research to clarify PFAS's role in CRC risk and progression. CONCLUSION: Evidence on the relationship between PFAS exposure and CRC risk remains limited and inconclusive. Large-scale, prospective epidemiological studies that incorporate biomarker-based exposure assessment, including pre-diagnostic PFAS levels, diverse populations, and rigorous study design are needed to clarify the role of PFAS in CRC development. Such research could provide the role of PFAS in CRC development and progression, guiding public health policies and support targeted interventions to reduce CRC risk.