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。第一个是在洛杉矶的非裔美国人和白种人中进行的肺癌遗传易感性的病例对照研究。我在南加州大学任教时进行了这项研究。在本研究中，我检测了大量与肺癌相关的遗传多态性。根据目前的标准，这项研究的规模不大，但对于检查常见的多态性仍然有价值。在这项研究中，我与NIEHS的道格拉斯贝尔（Douglas Bell）开始了一项合作，以检查与肺癌风险相关的P53反应基因的功能显著多态性。最近完成了实验室分析，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，研究与肺癌风险相关的炎症基因的变异，并进行全基因组扩增。查诺克博士的实验室很快就要开始实验了 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，汇集了许多肺癌研究，为研究基因-环境相互作用提供足够的力量。我是这个集资项目的顾问委员会成员。 第三项肺癌研究是与中国上海男性前瞻性队列研究的合作。这项研究是基于南加州大学。在过去的几年里，我一直在研究这个队列中肺癌的遗传、饮食和环境因素。我使用所谓的嵌套病例对照研究设计完成了这项工作。这使用了来自所有诊断的肺癌病例的样本和来自未患癌症的队列的匹配对照组。本研究的主要优势在于前瞻性设计和上海队列的独特暴露。我发表了关于基因-饮食相互作用（异硫氰酸酯和GSTM 1多态性）和IGF-1与上海队列肺癌相关的前瞻性研究。遗传学研究使用了从档案血清样本中提取的DNA，这带来了后勤挑战。最近，NCI将这项由外部资助的研究延长了五年的随访期。我写了拨款中关于肺癌的部分。获得资助的肺癌工作包括研究血清硒水平与硒蛋白多态性之间的相互作用，以及另一项研究黄曲霉毒素摄入量的生物标志物与DNA修复基因多态性之间的相互作用。这项研究是由校外资助的。 另一个组成项目是磁场暴露和乳腺癌风险的研究。这是一个嵌套的病例对照研究，我在南加州大学当教员的时候就开始用校外资金。从NIEHS开始，我继续运行这个项目，直到完成数据收集。该研究的主要论文发表于2003年，我不期望进一步研究磁场和癌症风险。 在其他乳腺癌研究中，我也是姐妹研究的合作者，参与了最初的概念。我正在牵头评估与交通有关的空气污染。我还增加了一些问题，这些问题可用于扩展队列的有用性，以包括非恶性呼吸系统疾病。

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.