Serum per- and polyfluoroalkyl substances in relation to circulating thyroxine levels and thyroid cancer risk: results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort

This study investigated whether serum levels of per- and polyfluoroalkyl substances (PFAS) are associated with circulating thyroxine levels and thyroid cancer within a cohort study with exposure levels comparable to that of the U.S. general population. We conducted a nested case-control study of thyroid cancer (189 cases, 378 individually matched controls) investigating serum concentrations of five PFAS within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) Cohort. Additionally, a meta-analysis of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in relation to thyroxine levels was performed across seven PLCO metabolomic investigations totaling 3,389 participants. Odds ratios (ORs) and 95% confidence intervals (CIs) relating thyroid cancer associations with serum PFAS concentrations were computed using multivariable conditional logistic regression. We analyzed thyroxine associations with PFOA and PFOS using study-specific multivariable linear regression models followed by random effects meta-analysis. We observed inverse associations with thyroid cancer for PFOA (fourth vs. first quartile: OR = 0.47, 95 % CI = 0.27, 0.80; P_trend = 0.0035) and PFOS (OR = 0.63; 95 % CI = 0.37, 1.06; P_trend = 0.092). These associations remained in analyses additionally adjusting for PFAS. No consistent evidence of a positive association with thyroid cancer was observed for other PFAS. In the meta-analysis, PFOA was positively associated with thyroxine (P = 0.006), including after adjustment for PFOS (P = 0.03). Our findings provide evidence in support of effects of some PFAS on thyroxine production, and against PFAS associations with increased thyroid cancer risk. These findings in a low-exposed population have important public health relevance, given their comparability in the distribution of serum PFAS concentrations to that of the general population.