Understanding determinants of racial disparities in lung cancer incidence

了解肺癌发病率种族差异的决定因素

基本信息

批准号：
10383735
负责人：
Melinda Aldrich
金额：
$ 62.36万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-07 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383735
关键词：
Address African American African American population Automobile Driving Behavioral Bioinformatics Biological Biological Assay Biometry Body mass index California Cancer Etiology Case-Control Studies Cellular biology Clinical Cohort Studies Collaborations Communities Complex DNA Data Diagnosis Disease Environmental Exposure Ethnic group Etiology European Fostering Gene Expression Genes Genetic Genetic Determinism Genetic Predisposition to Disease Genetic Risk Geographic Locations Goals Health Health behavior Histology Human Genetics In Vitro Incidence Individual Institutes Intervention Investigation Joints Knowledge Lead Lung diseases Malignant Neoplasms Malignant neoplasm of lung Mission Molecular Epidemiology National Cancer Institute Neighborhoods Pathway interactions Patients Play Policies Population Population Study Predisposition Prevention strategy Race Recommendation Risk Risk Factors Risk Reduction Rural San Francisco Smoker Smoking Socioeconomic Status Structure Tobacco smoking behavior Tobacco use Translating Universities Ursidae Family Validation Work behavioral health cancer epidemiology cancer health disparity cancer risk case control cigarette smoke community-level factor design disorder risk disparity reduction experience geographic disparity health disparity health disparity populations high risk improved innovation insight interdisciplinary approach light intensity lung cancer prevention men minority health disparity multidisciplinary neighborhood disadvantage novel polygenic risk score precision medicine predictive modeling prospective racial and ethnic racial determinant racial difference racial disparity recruit residential segregation sex social social determinants social health determinants sociodemographics study population transcriptome

项目摘要

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.

项目概要/摘要肺癌方面的显着种族差异是有据可查的，非裔美国人承受着更大的负担肺癌的发病率高于美国其他种族/族裔群体。虽然吸烟是一个重要的既定危险因素，但生物易感性和其他健康决定因素影响肺癌风险。非洲基于人群的研究美国人对肺癌危险因素的了解有限，因此对肺癌的了解甚少。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。解决肺癌种族差异复杂机制的知识差距发病率，我们建议评估肺癌发病率的生物学脆弱性和多层次病因以下具体目标：1）确定可能造成种族差异的新基因和生物途径肺癌发病率；2) 量化并建立决定因素（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 名肺癌病例和约 8,100 名对照者，略多于一半非裔美国人）招募自美国的四个地理区域我们的设计首先关注新的开创性的预测基因表达方法，通过生物信息学注释进行功能解释，以及强大的功能验证独立人群确定参与肺癌发病率的调节生物学机制将遗传发现转化为可解释的生物学背景。然后我们的项目研究了社区如何它可以在地理上构建种族差异（例如，居住隔离）以及个人层面行为、健康和社会决定因素（例如吸烟、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异研究所的使命，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层次因素（非洲美国人）。我们的项目促进了具有广泛知识的多学科团队之间的创新合作种族差异、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。该提案的一个关键创新方面是它与社区的合作伙伴关系咨询委员会将实证研究结果转化为肺癌预防建议。我们的调查结果多学科方法将产生持续影响，因为它将揭示精准医学的生物学途径机会并激励改进预防战略，以减少风险和差距。