DNA Methylation Profiles and Breast Cancer among WTC Survivors

2001年9月11日世界贸易中心的恐怖袭击和破坏 导致大量的灰尘，气体和烟雾释放，可能暴露于已知的， 对成千上万的人来说是致癌物。迄今为止，大多数研究都集中在 急救人员然而，世贸中心灾难对普通民众的影响， 特别是对妇女健康的了解仍然很少。 目前的申请将集中在妇女作为代表性不足的群体在以前的世贸组织- 相关研究。越来越多的数据表明，表观遗传变化可能是客观的， 暴露于环境化学物质的标志物。当前的应用程序将测试该假设 复杂的WTC暴露导致了明显的长期DNA甲基化变化， 在最初的世贸中心暴露后许多年才能检测到。项目的总体目标 是为了验证在WTC暴露的乳腺癌病例中观察到的DNA甲基化谱， 使用独立的暴露于WTC和未暴露于WTC的受试者组的初步研究。 将使用Illumina评估外周白色血细胞DNA中的总体DNA甲基化 Infinium MethylationEpic阵列可提供超过100个碱基的单碱基甲基化信息。 整个人类基因组中有850，000个胞嘧啶-磷酸-鸟嘌呤位点，是一种 表观基因组关联研究的全面解决方案。 预计该项目将有助于了解全球DNA的可能作用 甲基化作为世贸中心幸存者潜在致癌暴露客观标志 人口，特别是女性。本提案将解决在以下方面的知识差距： 世贸中心灾难对妇女幸存者影响。如果结果证实了 WTC暴露和改变DNA甲基化，这将导致新的发展， 可用于筛查和早期检测乳腺癌的客观生物标志物， 这是接触WTC的妇女中最常见的癌症。

The terrorist attacks and the destruction of the World Trade Center on September 11, 2001 resulted in the massive release of dust, gas, and fumes with potential exposure to known and suspected carcinogens for thousands of individuals. Most of the research to date focused on first-responders. However, the impact on the WTC disaster on the general population, particularly on women’s health remains poorly understood. The current application will focus on women as underrepresented group in previous WTC- related studies. Increasing data demonstrates that epigenetic changes may serve as objective markers of exposure to environmental chemicals. The current application will test the hypothesis that complex WTC exposures resulted in distinct long-term DNA methylation changes detectable many years after the original WTC exposure. The overarching objective of the project is to validate DNA methylation profiles of the WTC-exposed breast cancer cases observed in the pilot study using independent set of WTC-exposed and unexposed subjects. Global DNA methylation will be assessed in peripheral white blood cells DNA using Illumina Infinium MethylationEpic arrays which provide single-base methylation information for over 850,000 cytosine-phosphate-guanine sites throughout the human genome and is a comprehensive solution for epigenome-wide association studies. The project is expected to contribute to the understanding of the possible role of global DNA methylation as objective marker of potentially carcinogenic exposures among WTC survivor population, specifically women. The present proposal will address a knowledge gap on the impact of WTC disaster among women survivors. If the results confirm a correlation between WTC exposures and altered DNA methylation, it would lead to the development of novel objective biomarkers that could be used for screening and early detection of breast cancer, the most common cancer among WTC-exposed women.