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Grant Details

Grant Number: 5U19CA148127-04 Interpret this number
Primary Investigator: Amos, Christopher
Organization: Dartmouth College
Project Title: Transdisciplinary Research in Cancer of the Lung (TRICL)
Fiscal Year: 2013
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Abstract

Lung cancer is the leading cause of cancer-related mortality in the U.S. and the world. The genetic factors that commonly influence lung cancer susceptibility have not yet been investigated thoroughly, but eight genome-wide association studies have been performed. In area 1 of our response, we propose to integrate data from these eight studies that comprise over 13,000 lung cancer cases and 25,000 controls to increase power to detect genetic factors influencing all types of lung cancer and to allow us to analyze specific subsets, such as cases with early onset, specific histological sets, gender-defined groups and never smokers and the extended sample size will allow us to study gene-environment interactions. Existing genome-wide association studies have not analyzed data from nonCaucasian ethnic backgrounds and we therefore propose characterizing and fine mapping genetic factoid In 1500 African-American and 1500 Asian case-control pairs along with an additional 3000 Caucasian case-control pairs. We will then replicate our findings in a broader collection of an additional 12,000 case-control pairs. In area 2, we will evaluate genes in specific loci including nicotinic acetycholine receptor subunits CHRNA5 and CHRNA3 for the effiects that identified SNPs from area 1 have upon these genes functions. We will also study several other loci that have been identified through existing GWAS as strongly associated with lung cancer risk, including PSMA4, hTERT, CLPT1 ML, BAT3, and hMSHS. For each of these genes, we will study modulation of these genes using cellular models relevant to their known functions. In area 3, we propose epidemiological characterization of genetic and environmental risk factors for lung cancer. We will characterize mechanisms by which variation in the loci identified in area 1 influence risk, in conjunction with smoking and other exposures. We will also evaluate the calibration of existing risk prediction models for lung cancer and then develop new models based upon genetic and environmental data from this initiative. The overarching goal of our proposal is the identification of individuals at high risk for lung cancer development for whom screening and early detection would be most beneficial in reducing the burden of lung cancer.

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Publications

Telomere Structure And Maintenance Gene Variants And Risk Of Five Cancer Types
Authors: Karami S. , Han Y. , Pande M. , Cheng I. , Rudd J. , Pierce B.L. , Nutter E.L. , Schumacher F.R. , Kote-Jarai Z. , Lindstrom S. , et al. .
Source: International Journal Of Cancer, 2016-12-15 00:00:00.0; 139(12), p. 2655-2670.
PMID: 27459707
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Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
Authors: Fehringer G. , Kraft P. , Pharoah P.D. , Eeles R.A. , Chatterjee N. , Schumacher F.R. , Schildkraut J.M. , Lindström S. , Brennan P. , Bickeböller H. , et al. .
Source: Cancer Research, 2016-09-01 00:00:00.0; 76(17), p. 5103-14.
EPub date: 2016-09-01 00:00:00.0.
PMID: 27197191
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Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium.
Authors: Wang M. , Liu H. , Liu Z. , Yi X. , Bickeboller H. , Hung R.J. , Brennan P. , Landi M.T. , Caporaso N. , Christiani D.C. , et al. .
Source: Carcinogenesis, 2016 Sep; 37(9), p. 888-896.
EPub date: 2016-06-10 00:00:00.0.
PMID: 27288692
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A Novel Pathway-based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations
Authors: Qian D.C. , Han Y. , Byun J. , Shin H.R. , Hung R.J. , McLaughlin J.R. , Landi M.T. , Seminara D. , 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, 2016 Aug; 25(8), p. 1208-15.
PMID: 27222311
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Erratum To: Hierarchical Modeling Identifies Novel Lung Cancer Susceptibility Variants In Inflammation Pathways Among 10,140 Cases And 11,012 Controls
Authors: Brenner D.R. , Brennan P. , Boffetta P. , Amos C.I. , Spitz M.R. , Chen C. , Goodman G. , Heinrich J. , Bickeböller H. , Rosenberger A. , et al. .
Source: Human Genetics, 2016 Aug; 135(8), p. 963.
PMID: 27264937
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Functional Characterization Of Rad52 As A Lung Cancer Susceptibility Gene In The 12p13.33 Locus
Authors: Lieberman R. , Xiong D. , James M. , Han Y. , Amos C.I. , Wang L. , You M. .
Source: Molecular Carcinogenesis, 2016 May; 55(5), p. 953-63.
PMID: 26013599
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Novel Anti-crr9/clptm1l Antibodies With Antitumorigenic Activity Inhibit Cell Surface Accumulation, Pi3k Interaction, And Survival Signaling
Authors: Puskás L.G. , Mán I. , Szebeni G. , Tiszlavicz L. , Tsai S. , James M.A. .
Source: Molecular Cancer Therapeutics, 2016 May; 15(5), p. 985-97.
PMID: 26939707
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The Potential Utility Of Re-mining Results Of Somatic Mutation Testing: Kras Status In Lung Adenocarcinoma
Authors: Biernacka A. , Tsongalis P.D. , Peterson J.D. , de Abreu F.B. , Black C.C. , Gutmann E.J. , Liu X. , Tafe L.J. , Amos C.I. , Tsongalis G.J. .
Source: Cancer Genetics, 2016 May; 209(5), p. 195-8.
PMID: 27068338
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FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data.
Authors: Li Y. , Byun J. , Cai G. , Xiao X. , Han Y. , Cornelis O. , Dinulos J.E. , Dennis J. , Easton D. , Gorlov I. , et al. .
Source: Bmc Bioinformatics, 2016-03-09 00:00:00.0; 17, p. 122.
EPub date: 2016-03-09 00:00:00.0.
PMID: 26961892
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Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls.
Authors: Kang X. , Liu H. , Onaitis M.W. , Liu Z. , Owzar K. , Han Y. , Su L. , Wei Y. , Hung R.J. , Brhane Y. , et al. .
Source: Carcinogenesis, 2016 Mar; 37(3), p. 280-9.
PMID: 26905588
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Meta-analysis Of Genome-wide Association Studies Identifies Multiple Lung Cancer Susceptibility Loci In Never-smoking Asian Women
Authors: Wang Z. , Seow W.J. , Shiraishi K. , Hsiung C.A. , Matsuo K. , Liu J. , Chen K. , Yamji T. , Yang Y. , Chang I.S. , et al. .
Source: Human Molecular Genetics, 2016-02-01 00:00:00.0; 25(3), p. 620-9.
PMID: 26732429
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Gene By Environment Investigation Of Incident Lung Cancer Risk In African-americans
Authors: David S.P. , Wang A. , Kapphahn K. , Hedlin H. , Desai M. , Henderson M. , Yang L. , Walsh K.M. , Schwartz A.G. , Wiencke J.K. , et al. .
Source: Ebiomedicine, 2016 Feb; 4, p. 153-61.
PMID: 26981579
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Fine Mapping Of Chromosome 5p15.33 Based On A Targeted Deep Sequencing And High Density Genotyping Identifies Novel Lung Cancer Susceptibility Loci
Authors: Kachuri L. , Amos C.I. , McKay J.D. , Johansson M. , Vineis P. , Bueno-de-Mesquita H.B. , Boutron-Ruault M.C. , Johansson M. , Quirós J.R. , Sieri S. , et al. .
Source: Carcinogenesis, 2016 Jan; 37(1), p. 96-105.
PMID: 26590902
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A Cross-cancer Genetic Association Analysis Of The Dna Repair And Dna Damage Signaling Pathways For Lung, Ovary, Prostate, Breast, And Colorectal Cancer
Authors: Scarbrough P.M. , Weber R.P. , Iversen E.S. , Brhane Y. , Amos C.I. , Kraft P. , Hung R.J. , Sellers T.A. , Witte J.S. , Pharoah P. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Jan; 25(1), p. 193-200.
PMID: 26637267
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Focused Analysis of Exome Sequencing Data for Rare Germline Mutations in Familial and Sporadic Lung Cancer.
Authors: Liu Y. , Kheradmand F. , Davis C.F. , Scheurer M.E. , Wheeler D. , Tsavachidis S. , Armstrong G. , Simpson C. , Mandal D. , Kupert E. , et al. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2016 Jan; 11(1), p. 52-61.
PMID: 26762739
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Identification Of Shared And Unique Susceptibility Pathways Among Cancers Of The Lung, Breast, And Prostate From Genome-wide Association Studies And Tissue-specific Protein Interactions
Authors: Qian D.C. , Byun J. , Han Y. , Greene C.S. , Field J.K. , Hung R.J. , Brhane Y. , Mclaughlin J.R. , Fehringer G. , Landi M.T. , et al. .
Source: Human Molecular Genetics, 2015-12-20 00:00:00.0; 24(25), p. 7406-20.
PMID: 26483192
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Deciphering associations for lung cancer risk through imputation and analysis of 12,316 cases and 16,831 controls.
Authors: Wang Y. , Wei Y. , Gaborieau V. , Shi J. , Han Y. , Timofeeva M.N. , Su L. , Li Y. , Eisen T. , Amos C.I. , et al. .
Source: European Journal Of Human Genetics : Ejhg, 2015 Dec; 23(12), p. 1723-8.
PMID: 25804397
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Tert Polymorphism Rs2736100-c Is Associated With Egfr Mutation-positive Non-small Cell Lung Cancer
Authors: Wei R. , Cao L. , Pu H. , Wang H. , Zheng Y. , Niu X. , Weng X. , Zhang H. , Favus M.J. , Zhang L. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2015-11-15 00:00:00.0; 21(22), p. 5173-80.
PMID: 26149460
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Rna-seq Analysis Of Lung Adenocarcinomas Reveals Different Gene Expression Profiles Between Smoking And Nonsmoking Patients
Authors: Li Y. , Xiao X. , Ji X. , Liu B. , Amos C.I. .
Source: Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine, 2015 Nov; 36(11), p. 8993-9003.
PMID: 26081616
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The Role Of Haplotype In 15q25.1 Locus In Lung Cancer Risk: Results Of Scanning Chromosome 15
Authors: Ji X. , Gui J. , Han Y. , Brennan P. , Li Y. , McKay J. , Caporaso N.E. , Bertazzi P.A. , Landi M.T. , Amos C.I. .
Source: Carcinogenesis, 2015 Nov; 36(11), p. 1275-83.
PMID: 26282330
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Cross Cancer Genomic Investigation Of Inflammation Pathway For Five Common Cancers: Lung, Ovary, Prostate, Breast, And Colorectal Cancer
Authors: Hung R.J. , Ulrich C.M. , Goode E.L. , Brhane Y. , Muir K. , Chan A.T. , Marchand L.L. , Schildkraut J. , Witte J.S. , Eeles R. , et al. .
Source: Journal Of The National Cancer Institute, 2015 Nov; 107(11), .
PMID: 26319099
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Identification Of Lung Cancer Histology-specific Variants Applying Bayesian Framework Variant Prioritization Approaches Within The Tricl And Ilcco Consortia
Authors: Brenner D.R. , Amos C.I. , Brhane Y. , Timofeeva M.N. , Caporaso N. , Wang Y. , Christiani D.C. , Bickeböller H. , Yang P. , Albanes D. , et al. .
Source: Carcinogenesis, 2015 Nov; 36(11), p. 1314-26.
PMID: 26363033
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Genetic Determinants Of Telomere Length And Risk Of Common Cancers: A Mendelian Randomization Study
Authors: Zhang C. , Doherty J.A. , Burgess S. , Hung R.J. , Lindström S. , Kraft P. , Gong J. , Amos C.I. , Sellers T.A. , Monteiro A.N. , et al. .
Source: Human Molecular Genetics, 2015-09-15 00:00:00.0; 24(18), p. 5356-66.
PMID: 26138067
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New Mechanisms And Perspectives In Nicotine Withdrawal
Authors: Jackson K.J. , Muldoon P.P. , De Biasi M. , Damaj M.I. .
Source: Neuropharmacology, 2015 Sep; 96(Pt B), p. 223-34.
PMID: 25433149
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Rare, Low Frequency And Common Coding Variants In Chrna5 And Their Contribution To Nicotine Dependence In European And African Americans
Authors: Olfson E. , Saccone N.L. , Johnson E.O. , Chen L.S. , Culverhouse R. , Doheny K. , Foltz S.M. , Fox L. , Gogarten S.M. , Hartz S. , et al. .
Source: Molecular Psychiatry, 2015-08-04 00:00:00.0; , .
PMID: 26239294
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Allelic Spectra Of Risk Snps Are Different For Environment/lifestyle Dependent Versus Independent Diseases
Authors: Gorlov I.P. , Gorlova O.Y. , Amos C.I. .
Source: Plos Genetics, 2015 Jul; 11(7), p. e1005371.
PMID: 26201053
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Brca2-branching Out Too?
Authors: Spitz M.R. , Liu Y. , Amos C.I. .
Source: Journal Of The National Cancer Institute, 2015 May; 107(5), .
PMID: 25838449
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CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.
Authors: Chen L.S. , Hung R.J. , Baker T. , Horton A. , Culverhouse R. , Saccone N. , Cheng I. , Deng B. , Han Y. , Hansen H.M. , et al. .
Source: Journal Of The National Cancer Institute, 2015 May; 107(5), .
PMID: 25873736
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Dynamics Of Smoking-induced Genome-wide Methylation Changes With Time Since Smoking Cessation
Authors: Guida F. , Sandanger T.M. , Castagné R. , Campanella G. , Polidoro S. , Palli D. , Krogh V. , Tumino R. , Sacerdote C. , Panico S. , et al. .
Source: Human Molecular Genetics, 2015-04-15 00:00:00.0; 24(8), p. 2349-59.
PMID: 25556184
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Informed genome-wide association analysis with family history as a secondary phenotype identifies novel loci of lung cancer.
Authors: Poirier J.G. , Brennan P. , McKay J.D. , Spitz M.R. , Bickeböller H. , Risch A. , Liu G. , Le Marchand L. , Tworoger S. , McLaughlin J. , et al. .
Source: Genetic Epidemiology, 2015 Mar; 39(3), p. 197-206.
PMID: 25644374
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A recurrent mutation in PARK2 is associated with familial lung cancer.
Authors: Xiong D. , Wang Y. , Kupert E. , Simpson C. , Pinney S.M. , Gaba C.R. , Mandal D. , Schwartz A.G. , Yang P. , de Andrade M. , et al. .
Source: American Journal Of Human Genetics, 2015-02-05 00:00:00.0; 96(2), p. 301-8.
EPub date: 2015-02-05 00:00:00.0.
PMID: 25640678
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Nicotine Withdrawal
Authors: McLaughlin I. , Dani J.A. , De Biasi M. .
Source: Current Topics In Behavioral Neurosciences, 2015; 24, p. 99-123.
PMID: 25638335
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Meta-gsa: Combining Findings From Gene-set Analyses Across Several Genome-wide Association Studies
Authors: Rosenberger A. , Friedrichs S. , Amos C.I. , Brennan P. , Fehringer G. , Heinrich J. , Hung R.J. , Muley T. , Müller-Nurasyid M. , Risch A. , et al. .
Source: Plos One, 2015; 10(10), p. e0140179.
PMID: 26501144
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Prediction Of The Gene Expression In Normal Lung Tissue By The Gene Expression In Blood
Authors: Halloran J.W. , Zhu D. , Qian D.C. , Byun J. , Gorlova O.Y. , Amos C.I. , Gorlov I.P. .
Source: Bmc Medical Genomics, 2015; 8, p. 77.
PMID: 26576671
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Snp Characteristics Predict Replication Success In Association Studies
Authors: Gorlov I.P. , Moore J.H. , Peng B. , Jin J.L. , Gorlova O.Y. , Amos C.I. .
Source: Human Genetics, 2014 Dec; 133(12), p. 1477-86.
PMID: 25273843
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Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer.
Authors: Gao C. , Patel C.J. , Michailidou K. , Peters U. , Gong J. , Schildkraut J. , Schumacher F.R. , Zheng W. , Boffetta P. , Stucker I. , et al. .
Source: International Journal Of Epidemiology, 2016 06; 45(3), p. 896-908.
EPub date: 2016-07-17 00:00:00.0.
PMID: 27427428
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Gene characteristics predicting missense, nonsense and frameshift mutations in tumor samples.
Authors: Gorlov I.P. , Pikielny C.W. , Frost H.R. , Her S.C. , Cole M.D. , Strohbehn S.D. , Wallace-Bradley D. , Kimmel M. , Gorlova O.Y. , Amos C.I. .
Source: Bmc Bioinformatics, 2018-11-19 00:00:00.0; 19(1), p. 430.
EPub date: 2018-11-19 00:00:00.0.
PMID: 30453881
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DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort.
Authors: Sandanger T.M. , Nøst T.H. , Guida F. , Rylander C. , Campanella G. , Muller D.C. , van Dongen J. , Boomsma D.I. , Johansson M. , Vineis P. , et al. .
Source: Scientific Reports, 2018-11-13 00:00:00.0; 8(1), p. 16714.
EPub date: 2018-11-13 00:00:00.0.
PMID: 30425263
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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 Oct; 13(10), p. 1483-1495.
EPub date: 2018-07-04 00:00:00.0.
PMID: 29981437
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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity.
Authors: Ferreiro-Iglesias A. , Lesseur C. , McKay J. , Hung R.J. , Han Y. , Zong X. , Christiani D. , Johansson M. , Xiao X. , Li Y. , et al. .
Source: Nature Communications, 2018-09-25 00:00:00.0; 9(1), p. 3927.
EPub date: 2018-09-25 00:00:00.0.
PMID: 30254314
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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.
Authors: Ji X. , Bossé Y. , Landi M.T. , Gui J. , Xiao X. , Qian D. , Joubert P. , Lamontagne M. , Li Y. , Gorlov I. , et al. .
Source: Nature Communications, 2018-08-13 00:00:00.0; 9(1), p. 3221.
EPub date: 2018-08-13 00:00:00.0.
PMID: 30104567
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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, 2018-07-03 00:00:00.0; , .
EPub date: 2018-07-03 00:00:00.0.
PMID: 29971594
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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 00:00:00.0.
PMID: 29859855
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Sustained adrenergic signaling promotes intratumoral innervation through BDNF induction.
Authors: Allen J.K. , Armaiz-Pena G.N. , Nagaraja A.S. , Sadaoui N.C. , Ortiz T. , Dood R. , Ozcan M. , Herder D.M. , Haemerrle M. , Gharpure K.M. , et al. .
Source: Cancer Research, 2018-04-16 00:00:00.0; , .
EPub date: 2018-04-16 00:00:00.0.
PMID: 29661830
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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 00:00:00.0; 39(3), p. 336-346.
PMID: 29059373
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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 Feb; 57(2), p. 216-224.
EPub date: 2017-10-31 00:00:00.0.
PMID: 29071797
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Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium.
Authors: Lohavanichbutr P. , Sakoda L.C. , Amos C.I. , Arnold S.M. , Christiani D.C. , Davies M.P.A. , Field J.K. , Haura E.B. , Hung R.J. , Kohno T. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2017-12-15 00:00:00.0; 23(24), p. 7550-7557.
EPub date: 2017-10-03 00:00:00.0.
PMID: 28974547
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Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
Authors: Milne R.L. , Kuchenbaecker K.B. , Michailidou K. , Beesley J. , Kar S. , Lindström S. , Hui S. , Lemaçon A. , Soucy P. , Dennis J. , et al. .
Source: Nature Genetics, 2017 Dec; 49(12), p. 1767-1778.
EPub date: 2017-10-23 00:00:00.0.
PMID: 29058716
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Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.
Authors: Gu F. , Zhang H. , Hyland P.L. , Berndt S. , Gapstur S.M. , Wheeler W. , Ellipse Consortium T. , Amos C.I. , Bezieau S. , Bickeböller H. , et al. .
Source: International Journal Of Cancer, 2017-11-01 00:00:00.0; 141(9), p. 1794-1802.
EPub date: 2017-07-29 00:00:00.0.
PMID: 28699174
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Ancestry inference using principal component analysis and spatial analysis: a distance-based analysis to account for population substructure.
Authors: Byun J. , Han Y. , Gorlov I.P. , Busam J.A. , Seldin M.F. , Amos C.I. .
Source: Bmc Genomics, 2017-10-16 00:00:00.0; 18(1), p. 789.
EPub date: 2017-10-16 00:00:00.0.
PMID: 29037167
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