Serum levels of per- and polyfluoroalkyl substances (PFAS) and aggressive prostate cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Background/Aim: Per- and polyfluoroalkyl substances (PFAS) are group of chemicals commonly used in producing non-stick cookware, textiles, and firefighting foams. Exposure to PFAS is widespread in the U.S., with detectable serum levels in 98% of U.S. adults. Epidemiologic studies have suggested positive associations between PFAS and prostate cancer incidence and mortality, but the evidence is limited. We aimed to evaluate the association between pre-diagnostic serum concentrations of PFAS and aggressive prostate cancer risk in a large prospective study. Methods: We conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled participants from 1993-2001 from 10 U.S. centers. Cases (N=750) included men diagnosed with aggressive prostate cancer (Stage III/IV or Gleason score≥8) at least 1 year after the blood collection. Male controls (N=750) were individually matched to cases based on age, race/ethnicity, study center, year of blood collection, and vial type. Pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS), were measured. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between PFAS and prostate cancer risk. Results: Preliminary analyses showed null associations between serum PFAS concentrations and the risk of aggressive prostate cancer (e.g., PFOS: ORcontinuous = 0.93, 95% CI: 0.83-1.05). However, differences were observed by calendar year of blood draw, with later years (1998-2004) suggesting a positive association for some PFAS, such as PFHxS (ORcontinuous = 1.12, 95% CI: 1.01-1.46) and PFOS (ORcontinuous = 1.20, 95%CI: 0.97-1.49). Conclusions: This large prospective study did not provide evidence for an association between serum concentrations of individual PFAS and aggressive prostate cancer risk; however, an association among men with blood draws during later years, where measured serum PFAS concentrations were higher, cannot be ruled out.