Genetic And Environmental Factors In Lung Cancer

目的：本研究的目的是研究影响肺癌风险的遗传因素，并考虑与环境因素的相互作用。为此，我在两项研究中继续研究遗传易感性在肺癌病因学中的作用。第一个是洛杉矶县非裔美国人和白种人的病例对照研究。受试者登记（356例和731例对照受试者）由S. London在南加州大学担任教员期间完成。在过去的一年中，我们研究了几种DNA修复基因的多态性- XPD， XRCC1和XRCC3。我还参与了一个国际合作项目，汇集基因多态性和肺癌风险研究的原始数据，以提高检测基因-环境相互作用的能力。另一项研究是由nci资助的18244名上海男性进行的。这是为数不多的前瞻性收集血液和尿液样本的队列研究之一，并且有足够比例的吸烟者产生足够的肺癌病例。我们一直在对259例肺癌病例和匹配对照进行巢式病例对照研究。DNA来源来自血清，这带来了挑战，因为与全血相比，遗传物质的数量较少。在过去的一年里，我们研究了饮食摄入异硫氰酸酯的尿液生物标志物与参与其排泄的谷胱甘肽s转移酶基因多态性之间的关系。由于蔬菜来源的异硫氰酸盐的高摄入量，上海队列提供了一个独特的机会来检查这种基因-饮食相互作用。前瞻性收集的尿液样本使异硫氰酸盐的评估不受疾病过程的影响。我们还研究了肺癌风险与CYP1A1多态性之间的关系。我们目前正在分析与诊断前血清胰岛素样生长因子-1及其主要结合蛋白IGFBP-3水平相关的肺癌风险数据。这些样品是在NIEHS与Greg Travlos博士合作，经过广泛的实验室比较分析方法后进行分析的。由于该水平可能因疾病进程或治疗而改变，因此需要前瞻性分析的结果来评估其相关性。程序和技术：洛杉矶的病例对照研究采用标准的病例对照方法。人口控制从驾驶执照和医疗保险名单中登记。上海研究分析采用前瞻性队列中肺癌发病率的巢式病例对照研究。基因分型采用基于PCR的方法。成就：迄今为止，已有18篇关于非裔美国人和白种人基因多态性与肺癌风险的研究发表。在过去的一年里，我们有两篇关于DNA修复多态性和肺癌风险的论文被接受。在上海队列研究中，我们已经发表了异硫氰酸盐摄入量与GSTM1和GSTT1基因多态性之间基因-饮食相互作用的证据，这些基因多态性参与了GSTT1和GSTT1的代谢。我们对该队列中IGF-1和IGF1-BP3的分析代表了对这种关联的首次前瞻性观察。

Aims: The aim of this research is to examine genetic factors that influence the risk of lung cancer and to consider interactions with environmental factors. To this end, I continue to examine the role of genetic susceptibility in the etiology of lung cancer in two studies. The first is a case-control study of African-Americans and Caucasians in Los Angeles County. Subject enrollment (356 cases and 731 control subjects) was completed by S. London while she was a faculty member at the University of Southern California. During the past year, we have examined polymorphisms in several DNA repair genes - XPD, XRCC1 and XRCC3. I am also participating in an international collaborative project to pool original data from studies of genetic polymorphisms and lung cancer risk to improve power to examine gene-environment interactions. The other study is an NCI-funded cohort of 18,244 Shanghai men. This is one of the few cohort studies with prospectively collected blood and urine samples and an adequate proportion of smokers to yield sufficient lung cancer cases. We have been conducting nested case-control studies of 259 incident lung cancers and matched controls. The DNA source is from serum which presents challenges because of the smaller quantity of the genetic material compared to whole blood. In the past year we have examined the relation between a urinary biomarker of dietary intake of isothiocyanates and polymorphisms in glutathione S-transferase genes that are involved in their excretion. The Shanghai cohort offers a unique opportunity to examine this gene-diet interaction because of the high intake of vegetable sources of isothiocyanates. The prospectively collected urine samples enable assessment of isothiocyanates unbiased by effects of the disease process. We have also examined the relation between lung cancer risk and CYP1A1 polymorphisms. We are currently analyzing data on lung cancer risk in relation to prediagnostic serum levels of insulin-like growth factor-1 and its major binding protein IGFBP-3. These samples were analyzed at NIEHS in collaboration with Dr. Greg Travlos after extensive laboratory comparision of assay methods. Because levels may be altered by the disease process or treatment, results from prospective analyses are needed to evaluate the association. Procedures and techniques: The case-control study in Los Angeles uses standard case-control methodology. Population controls were enrolled from driver's licence and Medicare lists. The Shanghai study analyses use nested case control studies of incident lung cancer within the prospective cohort. Genotyping is done by PCR based methods. Accomplishments: A number of publications have emerged from the study of genetic polymorphisms and lung cancer risk in African-Americans and Caucasians - 18 to date. In the past year, we have had two manuscripts accepted on DNA repair polymorphisms and lung cancer risk. In the Shanghai cohort study, we have published evidence of a gene-diet interaction between isothiocyanate intake and genetic polymorphisms of GSTM1 and GSTT1 that are involved in their metabolism. Our analysis of IGF-1 and IGF1-BP3 in this cohort represents the first prospective look at this association.