Understanding determinants of racial disparities in lung cancer incidence

项目摘要/摘要 肺癌方面明显的种族差异是有据可查的，非裔美国人承担着更大的负担 与美国其他种族/民族相比，肺癌的发病率更高。虽然吸烟是一个关键的既定风险因素，但生物因素 易感性和其他健康决定因素会影响肺癌风险。非洲以人口为基础的研究 美国人对肺癌危险因素的了解一直有限，因此对肺癌的 导致肺癌种族差异的机制。我们假设肺癌存在种族差异 发病率是多方面的，是生物脆弱性和多层次健康之间相互作用的函数 决定因素。解决肺癌中种族差异的复杂机制的知识空白 发病率，我们建议评估生物脆弱性和肺癌发病率的多水平病因学 具体目标如下：1)确定可能导致种族差异的新基因和生物途径 肺癌发病率和2)量化和建立决定因素(遗传、行为、社会和 环境)导致肺癌发病率的种族差异。我们建议进行一项病例对照研究 肺癌(约5,300例肺癌病例和~8,100例对照，略高于一半的非裔美国人) 美国四个地理区域。我们的设计首先专注于新的开创性预测基因表达 方法，通过生物信息学注释进行功能解释，以及在 独立人群识别参与肺癌发病的调控生物机制 将遗传发现转化为可解释的生物学背景。然后我们的项目考察了社区是如何， 这可以在地理上构成种族差异(例如，居住隔离)以及个人水平 行为、健康和社会决定因素(如吸烟、肺部疾病、社会经济地位)可以 影响生物途径导致肺癌发病率的种族差异。该项目与 国家少数民族健康和健康差距研究所的使命，因为它审查了 导致健康差异人群肺癌发病率种族差异的多水平因素(非洲 美国人)。我们的项目促进了多学科团队之间的创新合作， 在种族差异、肺癌流行病学、健康的社会决定因素、生物统计学、细胞生物学、 人类遗传学和生物信息学。这项提议的一个关键创新方面是它与一个社区的伙伴关系 咨询委员会将把实证结果转化为预防肺癌的建议。来自我们的调查结果 多学科方法将产生持久的影响，因为它将揭示精确医学的生物途径 为减少风险和差距提供更好的机会和激励改进的预防战略。

PROJECT SUMMARY/ABSTRACT Striking racial disparities in lung cancer are well-documented, with African Americans bearing a greater burden of lung cancer than other U.S. racial/ethnic groups. While smoking is a key established risk factor, biologic susceptibility and other health determinants influence lung cancer risk. Population-based studies in African Americans to understand risk factors for lung cancer have been limited and as a result little is known about the mechanisms that cause racial disparities in lung cancer. We hypothesize racial disparities in lung cancer incidence are multifaceted and a function of the interplay between biologic vulnerability and multilevel health determinants. To address gaps in knowledge of the complex mechanisms of racial disparities in lung cancer incidence, we propose to assess biologic vulnerability and the multilevel etiology of lung cancer incidence with the following specific aims: 1) identify novel genes and biologic pathways which may underlie racial disparities in lung cancer incidence and 2) quantify and build a profile of determinants (genetics, behavioral, social, and environmental) contributing to racial disparities in lung cancer incidence. We propose a case-control study of lung cancer (~5,300 lung cancer cases and ~8,100 controls, slightly over half African American) recruited from four geographic regions across the U.S. Our design first focuses on new pioneering predicted gene expression approaches, functional interpretation via bioinformatics annotation, and robust functional validation in an independent population to identify regulatory biologic mechanisms involved in lung cancer incidence and translate genetic findings into an interpretable biologic context. Our project then examines how neighborhoods, which can structure racial disparities geographically, (e.g., residential segregation) along with individual-level behavioral, health, and social determinants (e.g., smoking, pulmonary disease, socioeconomic status) can influence biologic pathways to lead to racial disparities in lung cancer incidence. This project is relevant to the mission of the National Institute of Minority Health and Health Disparities since it examines the contribution of multi-level factors driving racial disparities in lung cancer incidence among a health disparity population (African Americans). Our project fosters innovative collaborations among a multidisciplinary team with extensive expertise in racial disparities, lung cancer epidemiology, social determinants of health, biostatistics, cell biology, human genetics, and bioinformatics. A key innovative aspect of this proposal is its partnership with a Community Advisory Board to move empirical findings into recommendations for lung cancer prevention. Findings from our multidisciplinary approach will have sustained impact since it will reveal biologic pathways for precision medicine opportunities and motivate improved preventive strategies for risk and disparities reductions.