Genetic and environmental factors in cancer

该项目包括两种癌症和几项研究。在肺癌方面，有三项研究。第一项是洛杉矶非裔美国人和高加索人肺癌遗传易感性的病例对照研究。我在南加州大学任教期间进行了这项研究。在这项研究中，我研究了大量与肺癌相关的基因多态。以目前的标准来看，这项研究的规模不大，但对于检查常见的多态现象仍然很有价值。在这项研究中，我与NIEHS的道格拉斯·贝尔开始了一项合作，以检查P53反应基因的功能显著多态与肺癌风险的关系。实验室分析最近已完成，我们将开始对这些数据进行流行病学分析。我还与NCI的Stephen Chanock博士合作，检查与肺癌风险相关的炎症相关基因的变异，并进行全基因组扩增。查诺克博士实验室的实验室工作很快就会开始。 第二项研究是一个汇集项目，我将我的肺癌数据贡献给一个合作研究，以汇集许多肺癌研究，为研究基因与环境的相互作用提供足够的动力。我是这个集合项目的顾问委员会的成员。 第三项肺癌研究是与上海男性前瞻性队列研究中国合作进行的。这项研究是在南加州大学进行的。在过去的几年里，我一直在这个队列中研究肺癌的遗传、饮食和环境因素。我用所谓的嵌套病例对照研究设计完成了这项工作。这使用了所有确诊的肺癌病例的样本和来自队列中尚未患上癌症的一组匹配的对照组的样本。这项研究的主要优势是前瞻性设计和上海队列的独特曝光。我已经在上海的队列中发表了关于基因-饮食相互作用(异硫氰酸盐和GSTM1多态)和IGF-1与肺癌关系的前瞻性研究。遗传学研究使用了从档案血清样本中提取的DNA，这在逻辑上提出了挑战。这项由外部资助的研究最近由NCI续签了五年的后续行动。我写了拨款中与肺癌有关的部分。受资助的肺癌工作包括研究血清硒水平与硒蛋白多态之间的相互作用，以及另一项研究黄曲霉毒素摄入与DNA修复基因多态之间的相互作用的生物标志物。这项研究是由外部资助的。 另一个组成部分的项目是关于磁场暴露和乳腺癌风险的研究。这是一项嵌套的病例对照研究，我是在南加州大学当教员时从外部资助开始的。在NIEHS，我继续运行这个项目，直到完成数据收集。这项研究的主要论文发表于2003年，我预计不会有关于磁场与癌症风险的进一步研究。 在其他乳腺癌研究中，我也是Sister研究的合作者，参与了最初的概念。我带头评估与交通有关的空气污染。我还增加了一些问题，可以用来扩大队列的有用性，将非恶性呼吸道疾病包括在内。

This project includes two cancers and several studies. In lung cancer, there are three studies. The first is a case-control study of genetic susceptibility to lung cancer in African-Americans and Caucasians in Los Angeles. I conducted this study while a faculty member at the University of Southern California. I have examined a large number of genetic polymorphisms relevant to lung cancer in this study. The study is of modest size by current standards, but is still valuable for examining common polymorphisms. I have initiated a collaboration with Douglas Bell at NIEHS to examine functionally significant polymorphisms in P53 response genes in relation to lung cancer risk in this study. Laboratory analyses were recently completed and we will begin epidemiologic analyses of these data. I am also collaborating with Dr. Stephen Chanock at NCI to examine variation in genes involved in inflammation in relation to lung cancer risk and to perform whole genome amplification. Laboratory work in Dr. Chanock's lab will being soon. A second study is a pooling project where I have contributed my lung cancer data to a collaborative study to pool across a number of lung cancer studies to provide sufficient power for studying gene-environment interactions. I serve on the advisory committee for this pooling project. The third lung cancer study is a collaboration with a prospective cohort study of men in Shanghai, China. This study is based at the University of Southern California. I have been investigating genetic, dietary and environmental factors for lung cancer in this cohort for the past several years. I have done this work using what is called a nested-case control study design. This uses samples from all diagnosed cases of lung cancer and a matched set of controls from the cohort who have not developed cancer. The major strengths of this study are the prospective design and the unique exposures of the Shanghai Cohort. I have published prospective studies of a gene-diet interaction (isothiocyanates and GSTM1 polymorphism) and IGF-1 in relation to lung cancer in the Shanghai Cohort. The genetic studies have used DNA extracted from archival serum samples which presents logistic challenges. This extramurally funded study has recently been renewed for an additional five years of follow-up by NCI. I wrote the portions of the grant dealing with lung cancer. The lung cancer work that was funded includes studying interactions between selenium levels in serum and polymorphisms in selenoproteins and another study of biomarkers of aflatoxin intake in interaction with polymorphisms in DNA repair genes. This study is extramurally funded. The other component project is a study of magnetic field exposure and breast cancer risk. This is a nested case-control study that I began with extramural funding while a faculty member at USC. From NIEHS, I continued to run this project until the completion of data collection. The main paper from the study was published in 2003 and I do not anticipate further work on magnetic fields and cancer risk. In other breast cancer research, I am also a collaborator on the Sister Study having been involved in the initial concept. I am taking the lead on assessment of traffic related air pollution in the cohort. I am also adding questions that can be used to extend the usefulness of the cohort to include nonmalignant respiratory disease.