The Effect of WTC Exposure on Thyroid Cancer in the Survivor Population

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Project Summary The reported two-fold excess risk of thyroid cancer in multiple World Trade Center (WTC) cohorts is not solely explained by overdiagnosis due to surveillance or physician bias. Endocrine disruptors (EDs), known to disrupt thyroid function and associated with thyroid carcinogenesis and cancer aggressiveness, have been found in WC dust samples. WTC dust-associated EDs’ exposure may potentially be associated with thyroid carcinogenesis and thyroid cancer aggressiveness via multiple pathways, in particular in children and adolescents exposed to the WTC dust during these critical developmental windows. Thyroid cancer in the WTC survivors’ population is largely unstudied and no study to date has investigated the potential impact of early life exposure to the WTC dust cloud on thyroid carcinogenesis and cancer aggressiveness. Using the WTC Environmental Health Center survivor population, including individuals who were <18 years at the time of WTC exposure, we aim to investigate the clinical, mutational, pathological, and inflammatory thyroid cancer profiles, hypothesizing that (early life) WTC exposure is associated with more aggressive thyroid cancer. First, we will perform an in-depth assessment comparing the clinical and mutational characteristics of WTC thyroid cancer to non-exposed controls (aim 1). Additionally, we will compare WTC thyroid cancer cases in the survivor population with unexposed control cancer cases to investigate the pathological features using computational modelling approaches (aim 2) and the gene expression profiles using Spatial Gene Expression (aim 3). We will perform a subgroup analysis of the individuals < 18 years at the time of WTC exposure. This study would be the first in-depth study to investigate thyroid cancer in the WTC survivor population, including an assessment of thyroid cancer in patients exposed as children or adolescents, integreting novel techniques including computational pathology modelling and Spatial Gene Expression. The proposed methods can easily be transposed to other solid cancers with increased risk in the WTC survivor population and to other environmentally exposed populations with increased cancer risk. Furthermore, identifying phenotypes and biomarkers associated with increased risk of more aggressive thyroid cancer will help identify patients needing more aggressive thyroid cancer screening and management and may lead to more effective health care delivery for this population.