Environmental chemical burden in differentiated thyroid cancer

Abstract

Differentiated thyroid cancer (DTC) incidence has increased over recent decades. Environmental risk factors may contribute, but little information is available on cumulative exposures to environmental chemicals in human thyroid tumors. This pilot study screened for and characterized environmental chemicals in DTC and non-cancer cadaver thyroid tissues, and explored differences in chemical profiles between tumor types as a secondary goal. Surgical samples from patients undergoing total or subtotal thyroidectomy for thyroid cancer in Atlanta, GA (USA) were procured from a biorepository (N = 60 representing three types: papillary thyroid carcinoma [PTC], follicular thyroid carcinoma [FTC], and invasive encapsulated follicular variant of PTC [IEFVPTC]; n = 20/type), along with cadaveric non-cancer thyroids for comparison (n = 8). An exposomics analysis was performed using gas chromatography–mass spectrometry to screen for chemicals from a library of 709 xenobiotic compounds. Overall, 442 environmental chemicals were annotated, including insecticides, herbicides, chemical synthesis intermediates, dye intermediates, flavoring or fragrance agents, plasticizers, solvents, combustion byproducts, fungicides, flame retardants, preservatives, polychlorinated biphenyls, lubricants, and per- and polyfluoroalkyl substances. Of these, 40 % were potential endocrine-disrupting chemicals. Twenty-nine identified chemicals differed between types; PTC samples in particular had higher levels of several combustion byproducts, insecticides and pesticides, and herbicides, many of which were known, likely, or possible carcinogens. However, no type-specific differences remained significant following correction for multiple comparisons. Two IARC Group 1 carcinogens, o-toluidine and 4-aminobiphenyl, were higher in tumors than in non-cancer thyroids. This study provides evidence for accumulation of environmental chemicals in human DTC and posits that specific pollutants may influence type-specific carcinogenesis. Larger and more geographically diverse cohorts are needed to determine the generalizability of these findings.