Per- and polyfluoroalkyl substances mixture exposure is associated with colorectal cancer TNM stage.

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.