||5U01CA253560-02 Interpret this number
||Vanderbilt University Medical Center
||Understanding Determinants of Racial Disparities in Lung Cancer Incidence
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.
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