WTC-Related Pollutants in Thyroid Cancer Tissue

项目摘要 据报道，世界贸易中心(WTC)的甲状腺癌发病率首次上升。 应答者的队列，并且没有证据表明监测或医生偏见是原因 发现增加了。此外，以前的研究结果表明，炎症在 呼吸性WTC粉尘暴露后的远处器官可能是共同的驱动途径 这增加了患癌症的风险。然而，到目前为止，还没有研究调查这种潜在的 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暴露的炎症和癌变的潜在(附加)驱动因素 人口。 WTC尘埃分析确定了各种不同的颗粒，包括金属，具有未知 对甲状腺的致癌作用。利用福尔马林固定石蜡的非靶向代谢组学- 包埋(FFPE)甲状腺癌组织样本，我们的目标是识别化学特征和 反映潜在机械作用的潜在感兴趣路径比较50个WTC- 暴露的甲状腺癌样本包括50个非WTC暴露的甲状腺癌样本和50个 良性甲状腺癌组织(目标1)。此外，我们还将使用 测量甲状腺组织中金属分布及其空间相关性的新方法 新鲜冰冻组织局部炎症标志物与5例WTC暴露甲状腺的比较 5例非WTC暴露的甲状腺癌标本和5例良性甲状腺癌标本 组织(目标2)。 这项研究将是第一次深入研究WTC粉尘的存在 人甲状腺癌组织中的成分和/或代谢物及其潜在的 与慢性组织炎症有关，这将提供关于 WTC暴露人群中甲状腺癌发病率增加的潜在途径 人口。所提出的方法可以很容易地转位到其他实体癌症 WTC人群风险增加，包括前列腺癌，以及人群研究 调查环境污染物是全球甲状腺癌增加的危险因素。 洞察环境污染物及其代谢物的存在和潜在的 甲状腺癌组织中相关的局部炎症是癌变的驱动因素 将塑造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.