Per- and polyfluoroalkyl substances and associated proteomic biomarker patterns of immuno-suppression and cell-proliferation in an adolescent population from Northern Norway: The Fit Futures Study

Per- and polyfluoroalkyl substances (PFAS) are stable man-made chemicals which are extensively used in the production of common consumer products. High human exposure has been associated with immunotoxicity. This study aimed to explore the relationship between PFAS exposure and proteomic biomarkers in a cross-sectional cohort of an adolescent population in northern Norway.This study included 839 adolescents. The serum concentration of 18 PFAS and 92 proteomic biomarkers were measured. Eight PFAS and 75 biomarkers were detected in >70% of the sample population, respectively. This study investigated these eight PFAS and 75 biomarkers. Factor analysis (FA) was used to reduce the dimensionality of the 75 biomarkers into factors/patterns. We applied a multivariate regression modelling by fitting factors as dependent variables with each of the PFAS as independent variables in separate models.Of the five factors extracted by the FA, Factor 2 loaded 10 biomarkers crucial in the development of innate and adaptive immunity. Factor 3 loaded five biomarkers which are important in mitogenic, cell-proliferation, and inflammation processes. Perfluorooctanesulfonate (PFOS), perfluoroundecanoate (PFUnDA), and perfluoroheptane sulfonate (PFHpS) were inversely associated with Factor 2: PFOS, (β= -0.26 [95% CI -0.42, -0.11]); PFUnDA, (β= -0.20 [95% CI -0.30, -0.10]); and PFHpS, (β= -0.17 [95% CI -0.28, -0.05]); while perfluorooctanoate (PFOA) was positively associated with Factor 3: PFOA, (β= 0.28 [95% CI 0.12, 0.44]).Exposure to PFOS, PFUnDA, and PFHpS were associated with biomarkers related to immunosuppression, while exposure to PFOA was associated with biomarkers related to carcinogenesis.