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

项目摘要 多个世界贸易中心（WTC）队列中报告的甲状腺癌两倍超额风险 不能仅仅用由于监督或医生偏见而导致的过度诊断来解释。内分泌 干扰物（EDs），已知可干扰甲状腺功能并与甲状腺癌发生有关 和癌症侵袭性，已经在WC灰尘样品中发现。WTC粉尘相关ED 暴露可能与甲状腺致癌和甲状腺癌有关 攻击性通过多种途径，特别是在儿童和青少年暴露于 在这些关键的发展窗口期间，世贸中心灰尘。 甲状腺癌在世贸中心幸存者的人口在很大程度上是未经研究的，没有研究迄今为止， 研究了早期暴露于世贸中心尘云对甲状腺的潜在影响。 致癌作用和癌症侵袭性。使用WTC环境健康中心 幸存者群体，包括WTC暴露时<18岁的个体，我们 目的研究甲状腺癌的临床、突变、病理和炎性特征， 假设（生命早期）WTC暴露与更具侵袭性的甲状腺癌相关。 首先，我们将进行深入评估，比较临床和突变 WTC甲状腺癌与非接触对照组的特征（目标1）。此外，我们将 将幸存者人群中的WTC甲状腺癌病例与未暴露的对照癌症病例进行比较 使用计算机建模方法研究病理特征的病例（目标2） 和使用空间基因表达的基因表达谱（aim 3）。我们将执行一个 对WTC暴露时< 18岁的个体进行亚组分析。 这项研究将是第一个深入研究甲状腺癌的世贸中心幸存者 包括评估儿童时期接触的患者的甲状腺癌， 青少年，整合新技术，包括计算病理学建模， 空间基因表达。所提出的方法可以很容易地转移到其他实体癌 WTC幸存者群体和其他环境暴露者的风险增加 癌症风险增加的人群。此外，识别表型和生物标志物 与更侵袭性的甲状腺癌风险增加相关，将有助于识别患者 需要更积极的甲状腺癌筛查和管理， 为这一人群提供有效的保健服务。

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.