Ecological Analysis of the Association Between 2,4-Dichlorophenoxyacetic Acid (2,4-D) Exposure and Thyroid Cancer Incidence in the United States

Abstract

Background/Objectives: The increasing incidence of thyroid cancer in the United States suggests a possible role for environmental exposures that potentially alter thyroid hormone regulation through cellular toxicity. 2,4-Dichlorophenoxyacetic acid (2,4-D) is a commonly used herbicide that can act as an endocrine disruptor and may be toxic to the thyroid gland. This ecological study examined county-level associations of 2,4-D use and age-adjusted incidence of thyroid cancer in the United States. Methods: The study utilized age-adjusted incidence rates for thyroid cancer for 2017–2021 through the CDC database. County-level 2,4-D use data was obtained from the U.S. Geological Survey and averaged over two time periods: 2003–2007 (10-year lag) and 2008–2012 (5-year lag). The association between 2,4-D use and thyroid cancer incidence was tested using linear mixed effects models. We further stratified the data analyses by sex and rurality (using the Rural–Urban Continuum Codes, RUCC 6–9 codes). For this study, statistical significance was set at p < 0.05. Results: In nationwide analyses, no significant associations were found in combined (5-year lag: p = 0.218; 10-year lag: p = 0.276) and sex-stratified models (males: p = 0.540 and p = 0.497; females: p = 0.222 and p = 0.353, for the 5- and 10-year lags, respectively). In analyses limited to rural counties, 2,4-D exposure was significantly associated with greater thyroid cancer incidence for both the 5-year (p = 0.004) and 10-year (p = 0.006) lag periods for the total population. Conclusions: The strong associations observed in rural counties suggest that agricultural context may influence the observed relationship between county-level 2,4-D use and thyroid cancer incidence. Additional mechanistic and longitudinal studies are required to establish causality and to elucidate underlying endocrine pathways.