Environmental Factors and Thyroid Cancer

Study Overview
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Brief Summary
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Thyroid cancer incidence has been steadily increasing and has nearly tripled since the 1970's in the US and worldwide. Early detection of small, papillary thyroid cancers using high quality diagnostic imaging explains only about 50% of this increased incidence, suggesting that there is a true increase in the occurrence of thyroid cancer and that changes in the prevalence of environmental risk factors might play a role in thyroid cancer etiology and progression. Yet, the cascade of environmental triggers linked to thyroid cancer remains elusive. 'Exposomics' studies all health relevant chemical exposures that an individual experiences, and leverages metabolomic platforms to estimate the internal environment, informing both exogenous exposures and the metabolic products that lead to, or arise from, disease. Besides exposure to ionizing radiation as known modifiable risk factor, epidemiological evidence suggests that exposure to endocrine disrupting chemicals may be a potential thyroid cancer risk factor due to their known effects on thyroid function. However, these studies relied either on exposure questionnaires which are susceptible to recall bias, or used a limited set of targeted biomarkers measured after diagnosis for testing associations with case-control status, and not thyroid cancer prognosis. Further, the molecular basis for observed associations with thyroid cancer remains unclear. To address the overall hypothesis that environmental exposures alter metabolic pathways and therefore affect thyroid cancer prognosis, small amounts of blood will be collected using dried blood microsampler technology (e.g. Mitra® sampling devices), which is minimally invasive and can be used to collect repeated blood measurements at home, without the need for specialized training. These dried blood samples will be used to perform metabolomics experiments, which describe the sum of exogenous exposures, metabolic alterations, and biological response. Additional exposure assessment will be performed using an exposure questionnaire. These results will be associated with thyroid cancer prognosis, e.g. disease-specific survival, disease recurrence, and mutational profiles, thus investigating the role of environmental exposures in the development of more aggressive forms of thyroid cancer.

Official Title
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The Role of Environmental Factors in Thyroid Cancer

Conditions
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Thyroid Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Bethesda category IV, V or VI following Fine Needle Aspiration; if a patient has a benign tumor following surgery, patient data/ samples will be stored to serve as benign control in potential future projects. Age 18 years and older Surgical candidate Ability to provide informed consent Exclusion criteria: History of thyroid cancer Completion surgery candidate Pregnant women or other vulnerable patients (e.g. wards of the state, prisoners)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed<br>High exposure to environmental pollutants | |
| Non-exposed<br>Low exposure to environmental pollutants | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phospholipids | Using Liquid Chromatography-High Resolution MS (LC-HRMS) analysis, exposure profiles will be ascertain for existing of combination(s) of plasma metabolites (endogenous and exogenous) that act synergistically to increase risk of non-familial, papillary thyroid cancer. Phospholipids is an endogenous metabolite | 4 years | 
| Ceramides | Using Liquid Chromatography-High Resolution MS (LC-HRMS) analysis, exposure profiles will be ascertain for existing of combination(s) of plasma metabolites (endogenous and exogenous) that act synergistically to increase risk of non-familial, papillary thyroid cancer. Ceramides is an endogenous metabolite | 4 years | 
| per-and polyfluoroalkyl substances (PFAS) | Using Liquid Chromatography-High Resolution MS (LC-HRMS) analysis, exposure profiles will be ascertain for existing of combination(s) of plasma metabolites (endogenous and exogenous) that act synergistically to increase risk of non-familial, papillary thyroid cancer. per-and polyfluoroalkyl substances (PFAS) is an exogenous metabolite | 4 years |