WTC-Related Pollutants in Thyroid Cancer Tissue

项目摘要 世界贸易中心（WTC）首次报告甲状腺癌发病率增加 应答者队列，没有证据表明监测或医生偏倚是其原因 发现炎症增加。此外，之前的研究结果表明， 呼吸道WTC粉尘暴露后的远端器官可能是共同的途径驱动 这增加了癌症风险。然而，迄今为止还没有研究调查过 WTC粉尘成分和/或其代谢物在远处器官中的积累，包括 甲状腺，作为WTC暴露人群中炎症和致癌作用的潜在（额外）驱动因素 人口。 世贸中心的灰尘分析确定了各种不同的颗粒，包括金属， 对甲状腺有致癌作用。使用福尔马林固定石蜡的非靶向代谢组学- 我们的目标是确定化学特征， 潜在的感兴趣的途径，反映了潜在的机械作用，比较50个WTC- 暴露的甲状腺癌样本与50个非WTC暴露的甲状腺癌样本和50个 良性甲状腺癌组织（目的1）。我们还将使用 一种测量甲状腺组织中金属分布及其空间相关性的新方法 新鲜冷冻组织中的局部炎症标志物比较5个暴露于WTC的甲状腺 癌症样本，5个非WTC暴露的甲状腺癌样本和5个良性甲状腺癌样本 组织（目标2）。 这项研究将是第一次深入研究调查世贸中心灰尘的存在 在人类甲状腺癌组织中的成分和/或其代谢物， 与慢性组织炎症的关系，这将提供关于 潜在的途径驱动甲状腺癌的发生率增加，在WTC暴露 人口所提出的方法可以很容易地转移到其他实体癌， WTC人群的风险增加，包括前列腺癌，以及人群研究 调查环境污染物作为全球甲状腺癌增加的危险因素。 深入了解环境污染物及其代谢物的存在， 甲状腺癌组织中相关的局部炎症作为致癌的驱动因素 将影响未来的流行病学环境癌症研究。

Project Summary There is an increased thyroid cancer incidence reported in the World Trade Center (WTC) first responder's cohorts and no evidence of surveillance or physician bias as the reason for this increase was found. Moreover, results from previous studies suggested that inflammation in distant organs following respiratory WTC dust exposure might be the common pathway driving this increased cancer risk. However, no research to date has investigated the potential accumulation of WTC dust components and/or their metabolites in distant organs, including the thyroid, as a potential (additional) driver of inflammation and carcinogenesis in WTC-exposed populations. WTC dust analyses identified a variety of different particles, including metals, with unknown carcinogenic effect on the thyroid. Using untargeted metabolomics of formalin-fixed paraffin- embedded (FFPE) thyroid cancer tissue samples, we aim to identify chemical profiles and potential pathways of interest reflecting a potential mechanistic action comparing 50 WTC- exposed thyroid cancer samples with 50 non-WTC exposed thyroid cancer samples and 50 benign thyroid cancer tissue (aim 1). We will additionally perform a subgroup analysis using a novel approach to measure the distribution of metals in thyroid tissue and the spatial association with markers of local inflammation in fresh frozen tissue comparing 5 WTC-exposed thyroid cancer samples with 5 non-WTC exposed thyroid cancer samples and 5 benign thyroid cancer tissue (aim 2). This study would be the first in-depth study to investigate the presence of WTC dust components and/or their metabolites in human thyroid cancer tissue and the potential association with chronic tissue inflammation, which would provide critical information about a potential pathway driving the increased thyroid cancer occurrence in the WTC-exposed population. The proposed methods can easily be transposed to other solid cancers with increased risk in the WTC population, including prostate cancer, as well as to population studies investigating environmental pollutants as risk factor for the global thyroid cancer increase. Insight in the presence of environmental pollutants and their metabolites and potentially associated local inflammation in thyroid cancer tissue as driving factors for carcinogenesis would shape future epidemiological environmental cancer research.