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

Abstract

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 (OR_adj) 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 (OR_adj, 1.56, 95% CI: 1.17-2.15, P = 0.004); results were similar when including patients with papillary thyroid cancer only (OR_adj, 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 (OR_adj, 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. Individual 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.

Funding: National Institutes of Health grants and The Andrea and Charles Bronfman Philanthropies.

Keywords: Environmental exposure; Multi-ethnic; Nested case-control study; Per- and polyfluoroalkyl substances (PFAS); Thyroid cancer.

Fig. 1

Association between log2-plasma PFAS concentrations and thyroid cancer in the total study population (n = 176; 88 cases vs. 88 pair-matched controls). OR: odds ratio; 95% CI: 95% confidence interval. Models adjusted for age, BMI, sex, race, and storage time of plasma sample. The P-values were derived from hypothesis testing procedures, specifically Wald tests, within the logistic regression models; P.adjusted: false discovery rate adjusted P-values by using the Benjamini and Hochberg method.

Fig. 2

Association between PFAS concentrations per increase in interquartile range (IQR) and thyroid cancer diagnosis (n = 176; 88 cases vs. 88 pair-matched controls). OR: odds ratio; 95% CI: 95% confidence interval. Models adjusted for age, BMI, sex, race, storage time of plasma sample. The P-values were derived from hypothesis testing procedures, specifically Wald tests, within the logistic regression models; P.adjusted: false discovery rate adjusted P-values by using the Benjamini and Hochberg method.

Fig. 3

Association between log2-plasma PFAS concentrations and papillary thyroid cancer (n = 148; 74 cases vs. 74 pair-matched controls). OR: odds ratio; 95% CI: 95% confidence interval. Models adjusted for age, BMI, sex, race, and storage time of plasma sample. The P-values were derived from hypothesis testing procedures, specifically Wald tests, within the logistic regression models; P.adjusted: false discovery rate adjusted P-values by using the Benjamini and Hochberg method.

Fig. 4

Association between PFAS concentrations per increase in interquartile range (IQR) and thyroid cancer diagnosis (n = 148; 74 cases vs. 74 pair-matched controls). OR: odds ratio; 95% CI: 95% confidence interval. Models adjusted for age, BMI, sex, race, storage time of plasma sample. The P-values were derived from hypothesis testing procedures, specifically Wald tests, within the logistic regression models; P.adjusted: false discovery rate adjusted P-values by using the Benjamini and Hochberg method.

Fig. 5

Association between log2-plasma PFAS concentrations and thyroid cancer diagnosis in the longitudinal study population (n = 62; 31 cases diagnosed ≥1 year after sample collection, 31 controls). OR: odds ratio; 95% CI: 95% confidence interval. Models adjusted for age, BMI, sex, race, and storage time of plasma sample. The P-values were derived from hypothesis testing procedures, specifically Wald tests, within the logistic regression models; P.adjusted: false discovery rate adjusted P-values by using the Benjamini and Hochberg method.

Fig. 6

Association between log2-plasma PFAS concentrations and thyroid cancer diagnosis in the cross-sectional study population (n = 114; 57 cases diagnosed <1 year after sample collection (prevalent cases), 57 controls). OR: odds ratio; 95% CI: 95% confidence interval. Models adjusted for age, BMI, sex, race, and storage time of plasma sample. The P-values were derived from hypothesis testing procedures, specifically Wald tests, within the logistic regression models; P.adjusted: false discovery rate adjusted P-values by using the Benjamini and Hochberg method.