Per- and polyfluoroalkyl substances (PFAS) exposure and thyroid cancer risk

Background Although per-and polyfluoroalkyl substances (PFAS) exposure is a potential contributor to the increasing thyroid cancer trend, limited studies have investigated the association between PFAS exposure and thyroid cancer in human populations. We therefore investigated associations between plasma PFAS levels and thyroid cancer diagnosis using a nested case-control study of patients with thyroid cancer with plasma samples collected at/before cancer diagnosis.Methods 88 patients with thyroid cancer using diagnosis codes and 88 healthy (non-cancer) controls pair-matched on sex, age (+/- 5 years), race/ethnicity, body mass index, smoking status, and year of sample collection were identified in the BioMe population (a medical record-linked biobank at the Icahn School of Medicine at Mount Sinai in New York); 74 patients had papillary thyroid cancer. Eight plasma PFAS were measured using untargeted analysis with liquid chromatography-high resolution mass spectrometry and suspect screening. Associations between individual PFAS levels and thyroid cancer were evaluated using unconditional logistic regression models to estimate adjusted odds ratios (ORadj) and 95% confidence intervals (CI).Findings There was a 56% increased rate of thyroid cancer diagnosis per doubling of linear perfluorooctanesulfonic acid (n-PFOS) intensity (ORadj, 1.56, 95% CI: 1.17-2.15, P = 0.004); results were similar when including patients with papillary thyroid cancer only (ORadj, 1.56, 95% CI: 1.13-2.21, P = 0.009). This positive association remained in subset analysis investigating exposure timing including 31 thyroid cancer cases diagnosed >= 1 year after plasma sample collection (ORadj, 2.67, 95% CI: 1.59-4.88, P < 0.001).Interpretation This study reports associations between exposure to PFAS and increased rate of (papillary) thyroid cancer. Thyroid cancer risk from PFAS exposure is a global concern given the prevalence of PFAS exposure. Indi-vidual PFAS studied here are a small proportion of the total number of PFAS supporting additional large-scale prospective studies investigating thyroid cancer risk associated with exposure to PFAS chemicals.