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Grant Details

Grant Number: 5U19CA203654-03 Interpret this number
Primary Investigator: Amos, Christopher
Organization: Baylor College Of Medicine
Project Title: Integrative Analysis of Lung Cancer Etiology and Risk
Fiscal Year: 2019
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Abstract

Abstract ? Overall Lung Cancer (LC) has been the most common cancer since 1985, resulting in over 1.8 million deaths worldwide per year. LC survival is dismal with a 5 year mortality of about 90%, largely because of its usual late stage diagnosis. Low dose CT (LDCT) reduces overall and lung cancer specific mortality among highly exposes smokers but yields excess positive findings and currently fails to identify many cases. This program project pursues a comprehensive and complementary set of research agendas to understand predictors of smoking and lung cancer. By integrating a comprehensive set of studies in the domains of smoking, genomics and biomarkers in the ILCCO, TRICL and LC3 consortia, and evaluating them together in the context of NLST and 5 other lung cancer screening trials, substantial progress can be made in early detection of lung cancer. Project 1: Genomic Predictors of Smoking Lung Cancer Risk studies large samples to identify uncommon variants, variants with low risk, and variants that affect risk through gene-environment interactions or through perturbations of pathways and further uses this information for studying environmental exposures. Project 2: Biomarkers of Lung Cancer Risk evaluates a wide range of risk biomarkers that have been implicated as promising lung cancer risk biomarkers, including miRNAs, metabolic, immune, protein, and epigenetic markers, using pre-diagnostic biospecimen from the Lung Cancer Cohort Consortium (LC3), and will identify a panel of validated risk biomarkers for use in risk prediction models Project 3: Translating Molecular and Clinical Data to Population Lung Cancer Risk Assessment establishes an integrated risk prediction model-based on lung cancer CT screening populations in US, Canada and Europe, combining personal health and exposure history, targeted molecular and genomic profiles and lung function data, and establishes comprehensive nodule assessment models for individuals with LDCT-detected non-calcified pulmonary nodules based on both diameter-based and volume-based probability models . These research studies are supported by integrating Administrative and Biostatistics cores. Efficiency is created from the scientific synergies among the projects and the use of shared samples and data. We believe that this level of integration across the P01 with three complementary projects working towards a unifying goal will yield novel observations about lung cancer development and provide unique translational opportunities to refine screening eligibility criteria and ultimately help improve screening efficiency and further reduce lung cancer mortality.

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Publications

Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region.
Authors: Hung R.J. , Spitz M.R. , Houlston R.S. , Schwartz A.G. , Field J.K. , Ying J. , Li Y. , Han Y. , Ji X. , Chen W. , et al. .
Source: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019 Aug; 14(8), p. 1360-1369.
EPub date: 2019-04-19.
PMID: 31009812
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Genome sequencing analysis identifies Epstein-Barr virus subtypes associated with high risk of nasopharyngeal carcinoma.
Authors: Xu M. , Yao Y. , Chen H. , Zhang S. , Cao S.M. , Zhang Z. , Luo B. , Liu Z. , Li Z. , Xiang T. , et al. .
Source: Nature genetics, 2019 Jul; 51(7), p. 1131-1136.
EPub date: 2019-06-17.
PMID: 31209392
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Global, pathway and gene coverage of three Illumina arrays with respect to inflammatory and immune-related pathways.
Authors: Tozzi V. , Rosenberger A. , Kube D. , Bickeböller H. .
Source: European journal of human genetics : EJHG, 2019-06-21; , .
EPub date: 2019-06-21.
PMID: 31227809
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ACAT: A Fast and Powerful p Value Combination Method for Rare-Variant Analysis in Sequencing Studies.
Authors: Liu Y. , Chen S. , Li Z. , Morrison A.C. , Boerwinkle E. , Lin X. .
Source: American journal of human genetics, 2019-03-07; 104(3), p. 410-421.
PMID: 30849328
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Efficient Variant Set Mixed Model Association Tests for Continuous and Binary Traits in Large-Scale Whole-Genome Sequencing Studies.
Authors: Chen H. , Huffman J.E. , Brody J.A. , Wang C. , Lee S. , Li Z. , Gogarten S.M. , Sofer T. , Bielak L.F. , Bis J.C. , et al. .
Source: American journal of human genetics, 2019-02-07; 104(2), p. 260-274.
EPub date: 2019-01-10.
PMID: 30639324
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Untouchable genes in the human genome: Identifying ideal targets for cancer treatment.
Authors: Gorlov I.P. , Gorlova O.Y. , Amos C.I. .
Source: Cancer genetics, 2019 Feb; 231-232, p. 67-79.
EPub date: 2019-01-24.
PMID: 30803560
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Shared heritability and functional enrichment across six solid cancers.
Authors: Jiang X. , Finucane H.K. , Schumacher F.R. , Schmit S.L. , Tyrer J.P. , Han Y. , Michailidou K. , Lesseur C. , Kuchenbaecker K.B. , Dennis J. , et al. .
Source: Nature communications, 2019-01-25; 10(1), p. 431.
EPub date: 2019-01-25.
PMID: 30683880
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Use of polygenic risk scores of nicotine metabolism in predicting smoking behaviors.
Authors: Chen L.S. , Hartz S.M. , Baker T.B. , Ma Y. , L Saccone N. , Bierut L.J. .
Source: Pharmacogenomics, 2018 12; 19(18), p. 1383-1394.
EPub date: 2018-11-16.
PMID: 30442082
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Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.
Authors: Rosenberger A. , Hung R.J. , Christiani D.C. , Caporaso N.E. , Liu G. , Bojesen S.E. , Le Marchand L. , Haiman C.A. , Albanes D. , Aldrich M.C. , et al. .
Source: International archives of occupational and environmental health, 2018 Nov; 91(8), p. 937-950.
EPub date: 2018-07-03.
PMID: 29971594
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Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins.
Authors: Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer , Guida F. , Sun N. , Bantis L.E. , Muller D.C. , Li P. , Taguchi A. , Dhillon D. , Kundnani D.L. , Patel N.J. , et al. .
Source: JAMA oncology, 2018-10-01; 4(10), p. e182078.
EPub date: 2018-10-11.
PMID: 30003238
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Rare Variants in Known Susceptibility Loci and Their Contribution to Risk of Lung Cancer.
Authors: Liu Y. , Lusk C.M. , Cho M.H. , Silverman E.K. , Qiao D. , Zhang R. , Scheurer M.E. , Kheradmand F. , Wheeler D.A. , Tsavachidis S. , et al. .
Source: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2018 10; 13(10), p. 1483-1495.
EPub date: 2018-07-04.
PMID: 29981437
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Genome-wide association study of familial lung cancer.
Authors: Byun J. , Schwartz A.G. , Lusk C. , Wenzlaff A.S. , de Andrade M. , Mandal D. , Gaba C. , Yang P. , You M. , Kupert E.Y. , et al. .
Source: Carcinogenesis, 2018-09-21; 39(9), p. 1135-1140.
PMID: 29924316
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Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma.
Authors: Wang Z. , Wei Y. , Zhang R. , Su L. , Gogarten S.M. , Liu G. , Brennan P. , Field J.K. , McKay J.D. , Lissowska J. , et al. .
Source: EBioMedicine, 2018 Jun; 32, p. 93-101.
EPub date: 2018-05-31.
PMID: 29859855
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Testing for gene-environment interaction under exposure misspecification.
Authors: Sun R. , Carroll R.J. , Christiani D.C. , Lin X. .
Source: Biometrics, 2018 06; 74(2), p. 653-662.
EPub date: 2017-11-09.
PMID: 29120492
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Testing for the indirect effect under the null for genome-wide mediation analyses.
Authors: Barfield R. , Shen J. , Just A.C. , Vokonas P.S. , Schwartz J. , Baccarelli A.A. , VanderWeele T.J. , Lin X. .
Source: Genetic epidemiology, 2017 12; 41(8), p. 824-833.
EPub date: 2017-10-29.
PMID: 29082545
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Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer.
Authors: Feng Y. , Wang Y. , Liu H. , Liu Z. , Mills C. , Owzar K. , Xie J. , Han Y. , Qian D.C. , Hung Rj R.J. , et al. .
Source: Molecular carcinogenesis, 2018 02; 57(2), p. 216-224.
EPub date: 2017-10-31.
PMID: 29071797
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Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.
Authors: Li Y. , Xiao X. , Han Y. , Gorlova O. , Qian D. , Leighl N. , Johansen J.S. , Barnett M. , Chen C. , Goodman G. , et al. .
Source: Carcinogenesis, 2018-03-08; 39(3), p. 336-346.
PMID: 29059373
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Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases.
Authors: McAllister K. , Mechanic L.E. , Amos C. , Aschard H. , Blair I.A. , Chatterjee N. , Conti D. , Gauderman W.J. , Hsu L. , Hutter C.M. , et al. .
Source: American journal of epidemiology, 2017-10-01; 186(7), p. 753-761.
PMID: 28978193
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Update on the State of the Science for Analytical Methods for Gene-Environment Interactions.
Authors: Gauderman W.J. , Mukherjee B. , Aschard H. , Hsu L. , Lewinger J.P. , Patel C.J. , Witte J.S. , Amos C. , Tai C.G. , Conti D. , et al. .
Source: American journal of epidemiology, 2017-10-01; 186(7), p. 762-770.
PMID: 28978192
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Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction.
Authors: Qian D.C. , Molfese D.L. , Jin J.L. , Titus A.J. , He Y. , Li Y. , Vaissié M. , Viswanath H. , Baldwin P.R. , Krahe R. , et al. .
Source: BMC genomics, 2017-09-19; 18(1), p. 740.
EPub date: 2017-09-19.
PMID: 28927378
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Opportunities and Challenges for Environmental Exposure Assessment in Population-Based Studies.
Authors: Patel C.J. , Kerr J. , Thomas D.C. , Mukherjee B. , Ritz B. , Chatterjee N. , Jankowska M. , Madan J. , Karagas M.R. , McAllister K.A. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2017 09; 26(9), p. 1370-1380.
EPub date: 2017-07-14.
PMID: 28710076
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Multiple phenotype association tests using summary statistics in genome-wide association studies.
Authors: Liu Z. , Lin X. .
Source: Biometrics, 2018 03; 74(1), p. 165-175.
EPub date: 2017-06-26.
PMID: 28653391
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A Decade of GWAS Results in Lung Cancer.
Authors: Bossé Y. , Amos C.I. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2018 04; 27(4), p. 363-379.
EPub date: 2017-06-14.
PMID: 28615365
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Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population.
Authors: Dong J. , Hu Z. , Wu C. , Guo H. , Zhou B. , Lv J. , Lu D. , Chen K. , Shi Y. , Chu M. , et al. .
Source: Nature genetics, 2012-07-15; 44(8), p. 895-9.
EPub date: 2012-07-15.
PMID: 22797725
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