Aug 2026· Frontiers in Toxicology· Vol 8· 1 citation· 40 references
Medicine
TL;DR
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.
Abstract
Environmental pollutants have been implicated in colorectal cancer risk, but the association between plasma per- and polyfluoroalkyl substance (PFAS) concentrations and TNM stage remains unclear. We recruited 110 patients with colorectal cancer in Beijing, China, between March and June 2024. Plasma concentrations of 32 PFAS were measured, and 23 PFAS with detection rates greater than 70% were included in the analysis. Random forest analysis was used to identify the highest-ranking PFAS for TNM-stage classification, followed by multivariable ordinal logistic regression and restricted cubic spline models to evaluate single-PFAS associations and concentration–response patterns. Bayesian kernel machine regression was further applied to assess the joint associations of the selected PFAS mixture, and stratified analyses were conducted by sex and age. PFOA and n-PFOS showed the highest median concentrations, at 2.899 ng/mL and 2.444 ng/mL, respectively. Random forest analysis identified PFPeS, PFTrDA, PFTeDA, HFPO-DA and 8:2 Cl-PFESA as five highest-ranking PFAS for TNM-stage classification. In single-pollutant models, HFPO-DA was positively associated with more advanced TNM stage (odds ratio 2.76, 95% confidence interval 1.39–5.46; P = 0.004), with a linear concentration–response association suggested by restricted cubic spline analysis (overall P = 0.012). Mixture analysis further indicated that higher combined PFAS concentrations were associated with more advanced TNM stage, with a more pronounced positive mixture–response pattern among female patients. These findings suggest 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.
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
Limiting to directly measured exposures, incorporating the full NHANES design in the primary regression, and triangulating across complementary mixture frameworks provide a more rigorous platform than prior single-pollutant or design-naive approaches.
Rifa Tasnia, E. Obeng-Gyasi· Journal of Xenobiotics· 0 citations
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
Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are persistent environmental pollutants with potential immunotoxic effects. Emerging epidemiological evidence suggests a link between PFAS exposure and autoimmune diseases, including rheumatoid arthritis (RA). However, the causal nature of this relationship remains unclear. Genetic instruments for circulating PFOA and PFOS levels were obtained from genome-wide association studies of European populations, while RA outcome data were sourced from the FinnGen consortium and United Kingdom Biobank. Associations were evaluated using multiple Mendelian randomization (MR) methods to assess the robustness of the findings. The inverse variance weighted method served as the primary approach. Additional methods, including MR-Egger, weighted median, simple mode, weighted mode, maximum likelihood estimation, and robust adjusted profile score, were applied to address potential pleiotropy and weak instrument bias. Sensitivity analyses, including Cochran Q-test for heterogeneity, MR-pleiotropy residual sum and outlier (MR-PRESSO) for pleiotropy detection, and leave-one-out analysis, were performed to validate the robustness of the findings. MR analysis identified a significant association between genetically predicted PFOA levels and increased RA risk (odds ratio = 1.87, 95% confidence interval [1.13–3.11], P = .015). Similarly, genetically predicted PFOS levels were positively associated with seropositive RA risk (odds ratio = 1.14, 95% confidence interval [1.00–1.29], P = .049). Sensitivity analyses confirmed the robustness of these findings, and reverse MR analysis did not indicate bidirectional causality. Our findings provide genetic evidence suggesting a potential association between PFAS exposure and RA risk. Given the widespread environmental persistence of PFAS, further investigation into potential health impacts and strategies to reduce exposure may be warranted. Further mechanistic studies are warranted to elucidate the biological pathways underlying the potential relationship between PFAS exposure and RA.
Per- and polyfluoroalkyl substances (PFAS) are pervasive organic compounds that have garnered significant attention due to their potential impacts on human health, particularly in relation to asthma, though current evidence remains limited. This study aimed to examine the association between PFAS exposure and adult asthma using a sample of 7106 participants aged 20 years and older from the NHANES survey, spanning 2003 to 2018. Survey-weighted multivariable logistic regression models, subgroup analysis, weighted quantile sum and Bayesian kernel machine regression models were employed to probe the relationship between PFAS and asthma. In the multivariable logistic regression analysis, higher log10-transformed perfluorooctane sulfonic acid (PFOS) and PFNA concentrations were significantly associated with lower odds of asthma (PFOS: OR = 0.76, 95% CI: 0.61–0.96; PFNA: OR = 0.77, 95% CI: 0.60–0.99). The inverse link between PFAS co-exposure and asthma incidence persisted across multi-pollutant models, weighted quantile sum regression, and Bayesian kernel machine regression models, with PFOS emerging as the primary negative influencer. In conclusion, this study highlights PFAS exposure is inversely associated with asthma risk in adults.
Tiankai Shan, Kai Wu, Jing-Xian Jiang· Medicine· 0 citations
The findings suggest that exposure to low levels of some alternative and precursor PFAS may be widespread in Canada and reinforce the role of pregnancy and breastfeeding as excretion pathways for legacy PFAS and support previous investigations demonstrating that exposure to some PFAS may be lower amongst financially disadvantaged populations.
Michael M. Borghese, Rebecca Lelievre, Sara Packull-McCormick et al.· Environmental Health· 0 citations