Integrative Analysis of Lung Cancer Etiology and Risk

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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.