DNA Methylation Profiles and Breast Cancer among WTC Survivors

2001年9月11日恐怖袭击和世贸中心被毁事件 导致粉尘、气体和烟雾的大量释放，潜在地暴露在已知和 对成千上万的人来说，疑似致癌物质。到目前为止，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， 特别是关于妇女健康的问题，人们仍然知之甚少。 目前的申请将侧重于妇女在前WTC中代表性不足的群体-- 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 暴露于环境化学品的标志物。目前的应用程序将检验这一假设 复杂的WTC暴露导致了不同的长期DNA甲基化变化 在最初的世贸中心暴露多年后才能检测到。该项目的总体目标 是为了验证暴露于WTC的乳腺癌病例的DNA甲基化图谱 这项先导性研究使用了一组独立的WTC暴露和未暴露的受试者。 将使用Illumina评估外周血白细胞DNA中的全球DNA甲基化 提供单碱基甲基化信息的Infinium甲基化史诗 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综合解决方案。 预计该项目将有助于理解全球DNA的可能作用 甲基化作为WTC存活者潜在致癌暴露的客观标志 人口，特别是女性。本提案将解决关于以下方面的知识差距 WTC灾难对女性幸存者的影响。如果结果证实了 WTC的暴露和DNA甲基化的改变，将导致新的 目的探讨可用于乳腺癌筛查和早期检测的生物标志物 在接触WTC的女性中最常见的癌症。

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.