Thyroid cancer incidence has been steadily increasing in the US and worldwide and multiple studies have highlighted the potential contribution of environmental exposures to this phenomenon. US military personnel who served in the Vietnam War represent a unique population of individuals highly exposed to Agent Orange, a widely used defoliant which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD, a persistent endocrine disrupting chemical with a long biological half-life of up to 10 years, has been classified as a human carcinogen. Previous studies have reported increased rates of thyroid cancer among Vietnam Veterans exposed to TCDD. The mechanism by which TCDD is thought to cause cancer is through a multi-step process leading to the accumulation of genetic changes (e.g., mutations and epigenetic changes) through continuous signaling associated with the long biological half-life of TCDD. Although it is known that these genetic changes may result in more aggressive cancer, no study to date has investigated the role of TCDD in thyroid cancer aggressiveness through this mechanism.

The current study therefore investigates whether past exposure to TCDD is associated with more aggressive thyroid cancer features, including higher rates of metastasis and cancer recurrence or lower survival, as well as more aggressive genetic changes. Results of this study will be directly applicable to improve current management protocols for thyroid cancer patients exposed to Agent Orange or TCDD. This may include the implementation of surveillance protocols following exposure as well as following surgery. Furthermore, treatment guidelines may be adapted, including the recommendation of a more extensive initial surgical procedure (e.g., complete instead of partial removal of the thyroid gland even for small, low-risk cancers) for thyroid cancer diagnosed in exposed patients.

Results of the current study will also greatly inform future research investigating risks associated with the increased exposure to other endocrine disrupting chemicals that are used in the military exposing active military personnel (e.g., flame retardants) as well as endocrine disrupting chemicals ubiquitously present in the environment exposing the general population (e.g., “forever chemicals”). The principle investigator of the current study is leading the thyroid cancer research program at the Department of Otolaryngology- Head and Neck Cancer at the Icahn School of Medicine at Mount Sinai with the main goal of investigating environmental exposures and thyroid cancer. The current study will therefore provide valuable information regarding a uniquely exposed population, which will shape future research studies initiated by the principle investigator and performed within the thyroid cancer research program.