Genetic And Environmental Factors In Lung Cancer

肺癌的遗传和环境因素

• 批准号: 6535054
• 负责人: STEPHANIE JOAN LONDON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 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/6535054
• 关键词: African American; Chinese; cancer risk; caucasian American; clinical research; cytochrome P450; dietary constituent; disease /disorder etiology; environment related neoplasm /cancer; enzyme activity; gene environment interaction; genetic polymorphism; genetic susceptibility; glutathione transferase; human genetic material tag; human subject; insulinlike growth factor; interview; isothiocyanates; lung neoplasms; neoplasm /cancer epidemiology; neoplasm /cancer genetics; polymerase chain reaction; questionnaires; racial /ethnic difference; tobacco abuse; urinalysis

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.

目的：这项研究的目的是检查影响肺癌风险并考虑与环境因素相互作用的遗传因素。为此，我继续研究两项研究中遗传易感性在肺癌病因中的作用。第一个是洛杉矶县对非裔美国人和高加索人的案例对照研究。 S. London在她是南加州大学的教职员工时完成了受试者招生（356例病例和731个对照科目）。在过去的一年中，我们检查了几个DNA修复基因的多态性-XPD，XRCC1和XRCC3。我还参加了一个国际协作项目，旨在从遗传多态性和肺癌风险的研究中汇集原始数据，以提高检查基因环境相互作用的能力。另一项研究是由18,244名上海男子组成的NCI资助的队列。这是为数不多的人群研究之一，该研究具有前瞻性收集的血液和尿液样本，并且有足够的吸烟者产生足够的肺癌病例。我们一直在进行259例事件肺癌和匹配对照的嵌套病例对照研究。 DNA来源来自血清，由于与全血相比，遗传物质的数量较少，因此提出了挑战。在过去的一年中，我们研究了与谷胱甘肽S-转移酶基因中的异硫氰酸酯饮食摄入量的尿生物标志物与涉及其排泄物的多态性之间的关系。上海队列提供了一个独特的机会来检查这种基因 - 迪埃特相互作用，因为异硫氰酸酯的蔬菜来源摄入量很高。前瞻性收集的尿液样品可以评估疾病过程的影响无偏见的异硫氰酸盐。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胰岛素样生长因子1及其主要结合蛋白IGFBP-3的肺癌风险相关的肺癌风险数据。经过广泛的实验室比较，在NIEHS与Greg Travlos博士合作分析了这些样品。由于疾病过程或治疗可能会改变水平，因此需要进行前瞻性分析的结果来评估该关联。程序和技术：洛杉矶的病例对照研究使用标准病例对照方法。人口控制是从驾驶执照和医疗保险列表中注册的。上海研究分析使用了前瞻性队列中入射肺癌的嵌套病例对照研究。基因分型通过基于PCR的方法完成。成就：非裔美国人和高加索人的遗传多态性和肺癌风险的研究已经出现了许多出版物-18岁。在过去的一年中，我们在DNA修复多态性和肺癌风险上接受了两种手稿。在上海队列研究中，我们发表了证明与其代谢有关的GSTM1和GSTT1的异硫氰酸酯摄入与遗传多态性之间存在基因 - 偏见相互作用的证据。我们对该队列中IGF-1和IGF1-BP3的分析代表了对该关联的第一个前瞻性研究。