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Grant Details

Grant Number: 5R01CA111703-05 Interpret this number
Primary Investigator: Chen, Chu
Organization: Fred Hutchinson Cancer Research Center
Project Title: Molecular Epidemiology of Lung Cancer
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): Tobacco smoke is the major cause of lung cancer, the most common type of fatal cancer worldwide. A possible means by which tobacco smoke exerts its carcinogenic effect is the DNA damage produced by the generation of reactive oxygen species and the formation of DNA adducts. Since the majority of persons who smoke tobacco do not develop lung cancer, it is possible that those who do develop this disease have a relatively poor capacity to repair the DNA damage that results from smoking. In a nested case-control study, we plan to determine whether polymorphisms of enzymes involved in the repair of smoking-induced DNA damage, namely those from the base excision (BER) and nucleotide excision repair (NER) pathways, are associated with risk of lung cancer. We propose to genotype the functional single nucleotide polymorphisms (SNPs) as well as tagging SNPs of 25 DNA repair genes (a total of 331 polymorphisms), that have been resequenced by the Seattle Variation Discovery Resource for the Environmental Genome Project. The lung cancer cases (n = 900) and controls (n = 1800) for the proposed study will come from the participants in the Carotene and Retinol Efficacy Trial (CARET) of lung cancer prevention. Genotyping of cases and controls will utilize DNA extracted from frozen whole blood samples. Detailed quantitative information on smoking and dietary history (using a food frequency questionnaire), obtained prior to the diagnosis of lung cancer, is available through CARET records. Cases and controls will be compared with respect to the prevalence of putative "high risk" genotypes, alone and in combination with other putative "high risk" genotypes within each pathway and in the two pathways combined. Analyses will also examine whether inferred haplotypes and their combinations are associated with risk. We will assess whether associations differ by histologic subtypes and sex. Results will be interpreted with multiple comparisons taken into account. The proposed study has sufficient statistical power to identify interactions between some of the high-risk genotypes/haplotypes, and to investigate whether the risk associated with a particular genotype/haplotype varies by other risk factors, such as smoking intensity and recency, and dietary factors, such as intake of antioxidant-rich fruits and vegetables (e.g. Rosaceae fruits and Cruciferae vegetables), and food-derived nutrients (e.g. carotenoids, vitamin C, and vitamin E).

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Publications

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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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; 9(1), p. 3927.
EPub date: 2018-09-25.
PMID: 30254314
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Methylation-derived Neutrophil-to-Lymphocyte Ratio and Lung Cancer Risk in Heavy Smokers.
Authors: Grieshober L. , Graw S. , Barnett M.J. , Thornquist M.D. , Goodman G.E. , Chen C. , Koestler D.C. , Marsit C.J. , Doherty J.A. .
Source: Cancer prevention research (Philadelphia, Pa.), 2018 11; 11(11), p. 727-734.
EPub date: 2018-09-25.
PMID: 30254071
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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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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; 9(1), p. 3221.
EPub date: 2018-08-13.
PMID: 30104567
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Telomere Length and Lung Cancer Mortality among Heavy Smokers.
Authors: Doherty J.A. , Grieshober L. , Houck J.R. , Barnett M.J. , Tapsoba J.D. , Thornquist M. , Wang C.Y. , Goodman G.E. , Chen C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2018 07; 27(7), p. 829-837.
EPub date: 2018-05-09.
PMID: 29743162
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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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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; 23(24), p. 7550-7557.
EPub date: 2017-10-03.
PMID: 28974547
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Functional variants in DCAF4 associated with lung cancer risk in European populations.
Authors: Liu H. , Liu Z. , Wang Y. , Stinchcombe T.E. , Owzar K. , Han Y. , Hung R.J. , Brhane Y. , McLaughlin J. , Brennan P. , et al. .
Source: Carcinogenesis, 2017-05-01; 38(5), p. 541-551.
PMID: 28383684
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Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of eight GWASs in the TRICL-ILCCO consortium.
Authors: Feng Y. , Wang Y. , Liu H. , Liu Z. , Mills C. , Han Y. , Hung R.J. , Brhane Y. , McLaughlin J. , Brennan P. , et al. .
Source: Scientific reports, 2017-04-11; 7(1), p. 825.
EPub date: 2017-04-11.
PMID: 28400551
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Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs.
Authors: Pan Y. , Liu H. , Wang Y. , Kang X. , Liu Z. , Owzar K. , Han Y. , Su L. , Wei Y. , Hung R.J. , et al. .
Source: Scientific reports, 2017-03-17; 7, p. 44634.
EPub date: 2017-03-17.
PMID: 28304396
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Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.
Authors: Yin J. , Liu H. , Liu Z. , Owzar K. , Han Y. , Su L. , Wei Y. , Hung R.J. , Brhane Y. , McLaughlin J. , et al. .
Source: Molecular carcinogenesis, 2017 06; 56(6), p. 1663-1672.
EPub date: 2017-02-23.
PMID: 28150878
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Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs.
Authors: Zhou F. , Wang Y. , Liu H. , Ready N. , Han Y. , Hung R.J. , Brhane Y. , McLaughlin J. , Brennan P. , Bickeböller H. , et al. .
Source: Molecular carcinogenesis, 2017 04; 56(4), p. 1227-1238.
EPub date: 2016-11-15.
PMID: 27805284
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A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.
Authors: Yuan H. , Liu H. , Liu Z. , Owzar K. , Han Y. , Su L. , Wei Y. , Hung R.J. , McLaughlin J. , Brhane Y. , et al. .
Source: Scientific reports, 2016-10-07; 6, p. 34234.
EPub date: 2016-10-07.
PMID: 27713484
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Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk.
Authors: Patel Y.M. , Park S.L. , Han Y. , Wilkens L.R. , Bickeböller H. , Rosenberger A. , Caporaso N. , Landi M.T. , Brüske I. , Risch A. , et al. .
Source: Cancer research, 2016-10-01; 76(19), p. 5768-5776.
EPub date: 2016-08-03.
PMID: 27488534
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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 09; 37(9), p. 888-896.
EPub date: 2016-06-10.
PMID: 27288692
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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. 280-289.
EPub date: 2016-02-10.
PMID: 26905588
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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.
EPub date: 2015-03-25.
PMID: 25804397
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Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
Authors: Wang Y. , McKay J.D. , Rafnar T. , Wang Z. , Timofeeva M.N. , Broderick P. , Zong X. , Laplana M. , Wei Y. , Han Y. , et al. .
Source: Nature genetics, 2014 Jul; 46(7), p. 736-41.
EPub date: 2014-06-01.
PMID: 24880342
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DNA repair genotype and lung cancer risk in the beta-carotene and retinol efficacy trial.
Authors: Doherty J.A. , Sakoda L.C. , Loomis M.M. , Barnett M.J. , Julianto L. , Thornquist M.D. , Neuhouser M.L. , Weiss N.S. , Goodman G.E. , Chen C. .
Source: International journal of molecular epidemiology and genetics, 2013; 4(1), p. 11-34.
EPub date: 2013-03-18.
PMID: 23565320
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Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.
Authors: Timofeeva M.N. , Hung R.J. , Rafnar T. , Christiani D.C. , Field J.K. , Bickeböller H. , Risch A. , McKay J.D. , Wang Y. , Dai J. , et al. .
Source: Human molecular genetics, 2012-11-15; 21(22), p. 4980-95.
EPub date: 2012-08-16.
PMID: 22899653
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Germ line variation in nucleotide excision repair genes and lung cancer risk in smokers.
Authors: Sakoda L.C. , Loomis M.M. , Doherty J.A. , Julianto L. , Barnett M.J. , Neuhouser M.L. , Thornquist M.D. , Weiss N.S. , Goodman G.E. , Chen C. .
Source: International journal of molecular epidemiology and genetics, 2012; 3(1), p. 1-17.
EPub date: 2012-02-05.
PMID: 22493747
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
Authors: Soler Artigas M. , Loth D.W. , Wain L.V. , Gharib S.A. , Obeidat M. , Tang W. , Zhai G. , Zhao J.H. , Smith A.V. , Huffman J.E. , et al. .
Source: Nature genetics, 2011-09-25; 43(11), p. 1082-90.
EPub date: 2011-09-25.
PMID: 21946350
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Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers.
Authors: Sakoda L.C. , Loomis M.M. , Doherty J.A. , Neuhouser M.L. , Barnett M.J. , Thornquist M.D. , Weiss N.S. , Goodman G.E. , Chen C. .
Source: Cancer causes & control : CCC, 2011 Mar; 22(3), p. 449-61.
EPub date: 2011-01-13.
PMID: 21229299
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