{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:38:29Z","timestamp":1787499509202,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>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\u2013response 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\u00a0ng\/mL and 2.444\u00a0ng\/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\u20135.46; P = 0.004), with a linear concentration\u2013response 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\u2013response 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.<\/jats:p>","DOI":"10.3389\/ftox.2026.1904192","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:56:51Z","timestamp":1786442211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Per- and polyfluoroalkyl substances mixture exposure is associated with colorectal cancer TNM stage"],"prefix":"10.3389","volume":"8","author":[{"given":"Ning","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Maternal and Child Health, School of Public Health, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Ministry of Education-Shanghai Key Laboratory of Children\u2019s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Ministry of Education-Shanghai Key Laboratory of Children\u2019s Environmental Health and Department of Developmental and Behavioural Paediatric and Child Primary Care, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengju","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, School of Public Health, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Ministry of Education-Shanghai Key Laboratory of Children\u2019s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s00216-022-04426-4","article-title":"A sensitive and robust method for the simultaneous determination of thirty-three legacy and emerging per- and polyfluoroalkyl substances in human plasma and serum","volume":"415","author":"Ao","year":"2023","journal-title":"Anal. 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