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Grant Details

Grant Number: 5U01CA253560-04 Interpret this number
Primary Investigator: Aldrich, Melinda
Organization: Vanderbilt University Medical Center
Project Title: Understanding Determinants of Racial Disparities in Lung Cancer Incidence
Fiscal Year: 2023


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.


Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study.
Authors: Duncan M.S. , Diaz-Zabala H. , Jaworski J. , Tindle H.A. , Greevy R.A. , Lipworth L. , Hung R.J. , Freiberg M.S. , Aldrich M.C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2024-04-03; 33(4), p. 500-508.
PMID: 38227004
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Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.
Authors: Middha P. , Thummalapalli R. , Betti M.J. , Yao L. , Quandt Z. , Balaratnam K. , Bejan C.A. , Cardenas E. , Falcon C.J. , Faleck D.M. , et al. .
Source: Nature communications, 2024-03-26; 15(1), p. 2568.
EPub date: 2024-03-26.
PMID: 38531883
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Minimum entropy framework identifies a novel class of genomic functional elements and reveals regulatory mechanisms at human disease loci.
Authors: Betti M.J. , Aldrich M.C. , Gamazon E.R. .
Source: bioRxiv : the preprint server for biology, 2023-12-12; , .
EPub date: 2023-12-12.
PMID: 37398170
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Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.
Authors: Middha P. , Thummalapalli R. , Betti M.J. , Yao L. , Quandt Z. , Balaratnam K. , Bejan C.A. , Cardenas E. , Falcon C.J. , Faleck D.M. , et al. .
Source: medRxiv : the preprint server for health sciences, 2023-09-13; , .
EPub date: 2023-09-13.
PMID: 37292751
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Sex modifies the effect of genetic risk scores for polycystic ovary syndrome on metabolic phenotypes.
Authors: Actkins K.V. , Jean-Pierre G. , Aldrich M.C. , Velez Edwards D.R. , Davis L.K. .
Source: PLoS genetics, 2023 May; 19(5), p. e1010764.
EPub date: 2023-05-31.
PMID: 37256887
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Racial Disparities in Lung Cancer Stage of Diagnosis Among Adults Living in the Southeastern United States.
Authors: Richmond J. , Murray M.H. , Milder C.M. , Blume J.D. , Aldrich M.C. .
Source: Chest, 2023 May; 163(5), p. 1314-1327.
EPub date: 2022-11-24.
PMID: 36435265
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Psychosocial impact of COVID-19 among adults in the southeastern United States.
Authors: Richmond J. , Sanderson M. , Shrubsole M.J. , Holowatyj A.N. , Schlundt D.G. , Aldrich M.C. .
Source: Preventive medicine, 2022 Oct; 163, p. 107191.
EPub date: 2022-08-11.
PMID: 35964774
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Inclusion of Smoking Data in Cardiovascular Disease Risk Estimation.
Authors: Duncan M.S. , Greevy R.A. , Tindle H.A. , Vasan R.S. , Lipworth L. , Aldrich M.C. , Lloyd-Jones D.M. , Freiberg M.S. .
Source: JAMA cardiology, 2022-02-01; 7(2), p. 195-203.
PMID: 34878493
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Disruption of medical care among individuals in the southeastern United States during the COVID-19 pandemic.
Authors: Ni B. , Gettler E. , Stern R. , Munro H.M. , Steinwandel M. , Aldrich M.C. , Friedman D.L. , Sanderson M. , Schlundt D. , Aronoff D.M. , et al. .
Source: Journal of public health research, 2021-09-24; 11(1), .
EPub date: 2021-09-24.
PMID: 34558253
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Immunotherapy-Mediated Thyroid Dysfunction: Genetic Risk and Impact on Outcomes with PD-1 Blockade in Non-Small Cell Lung Cancer.
Authors: Luo J. , Martucci V.L. , Quandt Z. , Groha S. , Murray M.H. , Lovly C.M. , Rizvi H. , Egger J.V. , Plodkowski A.J. , Abu-Akeel M. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2021-09-15; 27(18), p. 5131-5140.
EPub date: 2021-07-08.
PMID: 34244291
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A Call to Action: Dismantling Racial Injustices in Preclinical Research and Clinical Care of Black Patients Living with Small Cell Lung Cancer.
Authors: Thomas P.L. , Madubata C.J. , Aldrich M.C. , Lee M.M. , Owonikoko T.K. , Minna J.D. , Rudin C.M. , Sage J. , Lovly C.M. .
Source: Cancer discovery, 2021 Feb; 11(2), p. 240-244.
EPub date: 2020-12-14.
PMID: 33318034
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Defining Equity in Eligibility for Cancer Screening-Reply.
Authors: Aldrich M.C. , Blot W.J. , Blume J.D. .
Source: JAMA oncology, 2020-01-01; 6(1), p. 156-157.
PMID: 31697339
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