Integrative Analysis of Lung Cancer Etiology and Risk

项目总结/摘要 肺癌是世界范围内癌症的主要原因。死亡率占所有癌症的25%以上 死亡人数是美国乳腺癌死亡人数的四倍。尽管乳腺癌死亡人数有了实质性改善， 肺癌的治疗，其预后仍然令人沮丧，目前5年死亡率约为85%， 这在很大程度上是因为它通常在III或IV期被诊断出来。这种高肺癌负担反映了如何 普遍存在的是暴露于烟草烟雾和其他行为影响因素。这些暴露，沿着 筛查和癌症控制方法采用不当，阻碍了生存率的提高。肺管理 癌症风险可以在癌症预防连续体的所有步骤中实现，从初级预防开始， 主要是通过改变吸烟行为。肺癌的早期发现大大减少了 死亡率，但遵守现有的指导方针进行筛选是穷人。此外，大多数肺癌， 将在不适合筛查的人群中发生。最后，即使在那些接受筛查的人中， 发现了大量的积极发现，并改进了解决高风险与低风险发现的方法 以减轻过度管理和过度诊断的负担。我们的计划项目， “肺癌风险和病因学的综合分析（INTEGRAL）-应用和翻译正在扩大我们的 研究确定少数群体和从不吸烟者的预测风险因素。我们的目标是 以下.目的1：使用基因组预测因子识别肺癌高危人群 发展这一目标的重点是制定和应用不同人群的风险评估方法， 目的2：开发和实施新的生物标志物，以识别肺功能升高的个体 癌症风险，并将受益于低剂量螺旋CT筛查。这一目标将我们先前的研究扩展到 确定非吸烟者的风险，并评估生物标志物研究对基于人群的研究的转化。 目的3：基于综合分析评估肺癌检测和进展的预测因子 筛选人群的数据。本研究旨在评价生物标志物综合分析的新方法 以及筛查人群中的放射学标记研究。目标4：实施新的框架来管理 在肺癌发展和管理的各个阶段降低风险。这一目标贯穿各个项目 并评估将从研究中受益的人群的障碍和利益， 这是P01该提案建立在一个非常成功的先前计划项目的基础上， 研究、参与并将研究结果转化为不同的人群。

Project Summary/Abstract Lung cancer is the leading cause of cancer worldwide. The mortality rate represents over 25% of all cancers deaths, four times the number of breast cancer deaths in the U.S. Despite substantial improvements in the treatment of lung cancer, its prognosis remains dismal, with a current 5-year mortality of approximately 85%, in large part because it is usually diagnosed at stage III or IV. This high lung cancer burden reflects how ubiquitous are exposures to tobacco smoke and other behaviorally influenced factors. These exposures, along with poor adoption of screening and cancer control approaches, impedes improvements in survival. Management of lung cancer risk can be accomplished at all steps of the cancer prevention continuum, starting with primary prevention, primarily by modifying smoking behavior. After the development of lung cancer, early detection dramatically reduces mortality but compliance with existing guidelines for screening is poor. Furthermore, the majority of lung cancers that will develop occur among the population that is ineligible for screening. Finally, even among those who are screened, a large number of positive findings are detected and improved approaches to resolving high versus low-risk findings are needed to reduce the burden of excess management and overdiagnosis. Our program project, entitled ‘Integrative Analysis of Lung Cancer Risk and Etiology (INTEGRAL)-Applications and Translation is broadening our studies to identify predictive risk factors in minority populations and among never smokers. Our aims are the following. Aim 1: To use genomic predictors to identify individuals who are at higher risk for lung cancer development. This aim focuses on developing and applying methods for risk assessment in diverse populations, Aim 2: To develop and implement novel biomarkers that identify individuals who are at elevated lung cancer risk and will benefit from low dose spiral CT screening. This aim extends our prior research to identify risks for nonsmokers and evaluate the translation of biomarker studies for population-based research. Aim 3: To evaluate predictors of lung cancer detection and progression based on an integrative analysis of data from screening populations. This aim evaluates new approaches to integrative analysis of biomarker and radiographic marker studies in screening populations. Aim 4: To implement novel frameworks to manage risk reduction at all stages of lung cancer development and management. This aim cuts across projects and evaluates the barriers and interests of populations who will benefit from the research being conducted by this P01. This proposal builds upon a highly successful prior program project to broaden the populations we are studying and engage and translate the findings to diverse populations.