Jul 2026· Toxicology and Applied Pharmacology· Vol 514, pp.
117933
· 0 citations· 40 references
Medicine
TL;DR
Computational toxicology analyses indicated that PFAS may interact with endocrine- and growth factor-related pathways involving EGFR, AKT1, and ESR1, providing supportive but hypothesis-generating mechanistic context.
Abstract
Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with endocrine-disrupting and carcinogenic effects, but epidemiological evidence linking PFAS exposure to cancer remains inconsistent. We conducted a meta-analysis to systematically evaluate associations between PFAS exposure and risks of thyroid and breast cancer. Relevant literature published between January 2003 and May 2025 was retrieved from Web of Science and PubMed. The analysis showed that the pooled odds ratios (ORs) for perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) in relation to thyroid cancer were 0.87 (95% CI: 0.77-0.98) and 0.84 (95% CI: 0.75-0.94), respectively. In contrast, the pooled OR for overall PFAS exposure and breast cancer was 1.04 (95% CI: 1.00-1.09, I2 = 62.2%), indicating no statistically significant association but suggesting a borderline trend. Notably, PFAS exposure was inversely associated with invasive breast cancer (OR = 0.45, 95% CI: 0.26-0.76). Computational toxicology analyses indicated that PFAS may interact with endocrine- and growth factor-related pathways involving EGFR, AKT1, and ESR1, providing supportive but hypothesis-generating mechanistic context. This study highlights specific PFAS compounds that may be associated with altered risks of thyroid and breast cancer. Future high-quality prospective studies with standardized exposure assessments are warranted to clarify the potential carcinogenic effects of PFAS.
Per and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with endocrine-disrupting and carcinogenic potential. However, their bioaccumulation profiles and clinical relevance in human breast cancer remain largely unexplored.
In this preliminary study we quantified the absolute concentrations of 33 PFAS congeners (ng/g) in paired tumour and adjacent non-tumorous tissues from 11 breast cancer patients (
n
= 11) using LC–MS/MS to evaluate their tissue distribution and clinical correlations.
The detection rates for six compounds (HFPOTA, PFOA, PFNA, PFUnDA, PFOS, and 6:2Cl-PFESA) were greater than 40%. In paired samples, several congeners showed higher concentrations in tumour than in adjacent non-tumorous tissue; using a two-sided exact Wilcoxon signed-rank test with Hodges–Lehmann effect sizes, tumour enrichment remained significant after Benjamini–Hochberg correction for HFPOTA (
q
= 0.041), PFNA (
q
= 0.047) and PFUnDA (
q
= 0.047). HFPOTA showed by far the highest tissue burden (median 654 ng/g). Clinically, PFOS concentrations were descriptively higher in Luminal B than in Luminal A tumours and were positively correlated with the proliferation marker Ki-67; a high 6:2Cl-PFESA–PR rank correlation was observed in four samples but was not statistically significant on the raw p-value (p ≈ 0.051) and is exploratory. Bioinformatic analyses indicated that computationally predicted shared target genes of PFAS and breast cancer are enriched in the PPAR signaling pathway, lipid metabolism, and steroid hormone biosynthesis.
Collectively, PFAS bioaccumulation was associated with breast cancer clinicopathological characteristics. Because the target genes are predicted rather than experimentally validated and the cohort is small (
n
= 11), these are exploratory, hypothesis-generating findings that require validation in larger cohorts. This study underscores the need to reassess the biosafety of novel PFAS alternatives and provides new insights into the environmental etiology of breast cancer.
Bei Sun, Zhanhua Gao, Xiyue Liu et al.· Frontiers in Public Health· 0 citations
It is suggested that higher plasma PFAS concentrations, particularly HFPO-DA, may be associated with more advanced TNM stage in colorectal cancer and warrant confirmation in larger prospective studies.
Ning Kang, Yang Zhao, Zhi Huang et al.· Frontiers in Toxicology· 1 citation
Current evidence supports that an association exists between select chemical exposures and TC development, but study limitations prevent any direct link to causation.
Rachael Caretti, H. Arain, Herbert Chen· The Oncologist· 0 citations
Occupational PAH exposure is modestly associated with upper gastrointestinal cancer risk, particularly esophageal cancer, with higher risk estimates observed in high-exposure occupations.
M. S. Seyyedsalehi, Anna Vrtev, M. Lanza et al.· European Journal of Cancer P...· 0 citations
Background Alzheimer's disease (AD) is a prevalent neurodegenerative disorder among the elderly, influenced by both genetic and environmental factors. Organochlorine pesticides (OCPs) have recently been identified as potential environmental risk factors due to their bioaccumulation in adipose tissue and neurotoxic properties. Objective This systematic review aimed to examine the human evidence regarding exposure to OCPs and the risk of AD. The results of the meta-analysis showed that exposure to pesticides is significantly associated with an increased risk of AD. Methods A comprehensive search was performed across major scientific databases, including PubMed/MEDLINE, Scopus, Web of Science, the Cochrane Library, and Embase. Results Pooled estimates (random effects meta-analysis) of the four eligible studies showed a significant positive association between exposure to OCPs and the risk of AD (OR = 2.19; 95% CI: 1.40–3.42). These findings indicate that exposure to OCPs may significantly increase the risk of AD. The substantial heterogeneity among studies (I2 = 84.58%) may partly reflect differences in exposure assessment approaches, such as biomonitoring-based measurements compared with occupational or geographically inferred exposure assessments. Conclusions These findings highlight the importance of controlling occupational and environmental exposures to pesticides in preventing neurodegenerative outcomes. The findings suggest that chronic exposure to lipophilic pesticides, particularly persistent chlorinated compounds, may contribute to neurodegenerative processes implicated in the pathophysiology of AD. Therefore, more studies with similar designs and more precise exposure measurements are needed to confirm the results and reduce the heterogeneity.
Z. Ghaedrahmat, Farnaz Almasi, Javad Shamsi Goushki et al.· Journal of Alzheimer's Disea...· 0 citations
This pilot study provides some of the first estimates of PFAS exposure among prostate cancer patients in serum and tap water, showing moderate correlations between tap water and serum concentrations of specific PFAS analytes.
Stefanie A. Joseph, Chidinma Opara, Megan R. Shanahan et al.· medRxiv· 0 citations
