Environmental Exposure and DNA Damage

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广泛感兴趣。 表观遗传修饰，包括DNA甲基化，正越来越多地被认为是基因转录调控的重要决定因素，具有遗传性和获得性特征。 异常的DNA甲基化模式是癌变过程中最早和最常见的事件之一，最近的研究表明，与无疾病的女性相比，患有活动性卵巢癌的女性外周血替代组织的DNA表观遗传特征可能不同。 我们对900多名女性的外周血样本进行了全基因组DNA甲基化分析，以研究DNA甲基化模式是否与乳腺癌风险相关。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。 改变的miRNA表达是癌症的中心特征，并且已经显示miRNA表达特征与诊断、分期、预后和对治疗的反应相关。 癌症的表达模式显示出高组织特异性，使其成为癌症筛查的潜在标志物。 乳腺癌特异性miRNAs已被证明与分期、血管浸润、增殖指数和ER/PR状态相关。 最近，已经在人血浆和血清中发现了足够水平的miRNA以允许谱分析，具有足够的能力来区分患有转移性前列腺癌的男性与没有癌症的男性和患有卵巢癌的女性。 我们最近使用姐妹研究队列完成了对来自病例和非病例的400多份血清样本的检测，目前正在进行数据分析。

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.