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Environmental Exposure and DNA Damage

环境暴露和 DNA 损伤

基本信息

批准号：
8553715
负责人：
JACK A TAYLOR
金额：
$ 113.16万
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8553715
关键词：
Aberrant DNA Methylation Area Biological Assay Blood Vessels Blood specimen Cancer Etiology Characteristics Clinical Research Cohort Studies DNA Damage DNA Fingerprinting DNA Methylation DNA Modification Process Data Analyses Detection Diagnosis Disease Early Diagnosis Environmental Exposure Environmental Risk Factor Epidemiologic Studies Epigenetic Process Event Gene Targeting Genes Genetic Human Laboratories Malignant Neoplasms Malignant neoplasm of ovary Metastatic Prostate Cancer Methylation MicroRNAs Modification Molecular Molecular Profiling Pattern Plasma Prevention Process Research Research Design Risk Sampling Screening for cancer Serum Sister Site Specificity Staging Testing Tissues Transcriptional Regulation Woman cancer risk carcinogenesis environmental agent genome-wide indexing interest malignant breast neoplasm men outcome forecast peripheral blood response tool

项目摘要

Our laboratory is broadly interested in both genetic and epigenetic modifications associated with exposure and cancer. Epigenetic modifications, including DNA methylation, are being increasingly recognized as is being recognized as important determinants of gene transcriptional regulation that have both heritable and acquired characteristics. Aberrant DNA methylation patterns are among the earliest and most common events in carcinogenesis and recent studies suggest that the epigenetic profile of DNA from a surrogate tissue, peripheral blood, may differ between women with active ovarian cancer compared to women without disease. We have employed genome-wide profiling of DNA methylation in peripheral blood samples from more than 900 women in order to investigate whether the pattern of DNA methylation is associated with breast cancer risk. We have identified a number of methylation sites that are associated with increased risk and are continuing data analysis. A second form of epigenetic modification is miRNA expression. Altered miRNA expression is a central feature of cancer and miRNA expression signatures have been shown to be associated with diagnosis, stage, prognosis, and response to treatment. Expression patterns for cancer show high tissue specificity making them potential markers for cancer screening. Breast cancer specific miRNAs have been shown to correlate with stage, vascular invasion, proliferative index, and ER/PR status. Recently, sufficient levels of miRNAs have been found in human plasma and serum to permit profiling, with sufficient power to distinguish men with metastatic prostate cancer from men without cancer and women with ovarian cancer. We have recently completed assays on more than 400 serum samples from cases and non-cases using the Sister Study cohort and are in the process of data analysis.

我们的实验室对与暴露和癌症相关的遗传和表观遗传修饰都很感兴趣。表观遗传修饰，包括DNA甲基化，正日益被认为是具有遗传和获得性特征的基因转录调控的重要决定因素。异常的DNA甲基化模式是癌症发生中最早和最常见的事件之一，最近的研究表明，来自替代组织(外周血)的DNA的表观遗传学特征可能在患有活动性卵巢癌的女性与未患疾病的女性之间存在差异。我们对900多名女性的外周血样本进行了DNA甲基化的全基因组图谱分析，以调查DNA甲基化模式是否与乳腺癌风险有关。我们已经确定了一些与风险增加相关的甲基化位点，并正在继续进行数据分析。表观遗传修饰的第二种形式是miRNA表达。MiRNA表达改变是癌症的中心特征，miRNA表达特征已被证明与诊断、分期、预后和治疗反应有关。癌症的表达模式显示出高度的组织特异性，使其成为癌症筛查的潜在标记物。乳腺癌特异性miRNAs已被证明与分期、血管侵犯、增殖指数和ER/PR状态相关。最近，在人类血浆和血清中发现了足够水平的miRNAs，从而可以进行图谱分析，从而有足够的能力区分患有转移性前列腺癌的男性和没有癌症的男性和患有卵巢癌的女性。我们最近使用Sister研究队列完成了来自病例和非病例的400多个血清样本的分析，并正在进行数据分析。