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Grant Details

Grant Number: 7U19CA148127-03 Interpret this number
Primary Investigator: Amos, Christopher
Organization: Dartmouth College
Project Title: Transdisciplinary Research in Cancer of the Lung (TRICL)
Fiscal Year: 2012
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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

Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue.
Authors: Shi J, Marconett CN, Duan J, Hyland PL, Li P, Wang Z, Wheeler W, Zhou B, Campan M, Lee DS, Huang J, Zhou W, Triche T, Amundadottir L, Warner A, Hutchinson A, Chen PH, Chung BS, Pesatori AC, Consonni D, Bertazzi PA, Bergen AW, Freedman M, Siegmund KD, Berman BP, Borok Z, Chatterjee N, Tucker MA, Caporaso NE, Chanock SJ, Laird-Offringa IA, Landi MT
Source: Nat Commun, 2014 Feb 27;5, p. 3365.
EPub date: 2014 Feb 27.
PMID: 24572595
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A network-based kernel machine test for the identification of risk pathways in genome-wide association studies.
Authors: Freytag S, Manitz J, Schlather M, Kneib T, Amos CI, Risch A, Chang-Claude J, Heinrich J, Bickeböller H
Source: Hum Hered, 2013;76(2), p. 64-75.
EPub date: 2014 Jan 14.
PMID: 24434848
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Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data.
Authors: Tang H, Wei P, Duell EJ, Risch HA, Olson SH, Bueno-de-Mesquita HB, Gallinger S, Holly EA, Petersen G, Bracci PM, McWilliams RR, Jenab M, Riboli E, Tjĝnneland A, Boutron-Ruault MC, Kaaks R, Trichopoulos D, Panico S, Sund M, Peeters PH, Khaw KT, Amos CI, Li D
Source: Carcinogenesis, 2014 Feb 10;null, p. null.
EPub date: 2014 Feb 10.
PMID: 24419231
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CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis.
Authors: James MA, Vikis HG, Tate E, Rymaszewski AL, You M
Source: Cancer Res, 2014 Feb 15;74(4), p. 1116-27.
EPub date: 2013 Dec 23.
PMID: 24366883
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A genome-wide gene-gene interaction analysis identifies an epistatic gene pair for lung cancer susceptibility in Han Chinese.
Authors: Chu M, Zhang R, Zhao Y, Wu C, Guo H, Zhou B, Lu J, Shi Y, Dai J, Jin G, Ma H, Dong J, Wei Y, Wang C, Gong J, Sun C, Zhu M, Qiu Y, Wu T, Hu Z, Lin D, Shen H, Chen F
Source: Carcinogenesis, 2014 Mar;35(3), p. 572-7.
EPub date: 2013 Dec 9.
PMID: 24325914
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Dynamics of the risk of smoking-induced lung cancer: a compartmental hidden markov model for longitudinal analysis.
Authors: Chadeau-Hyam M, Tubert-Bitter P, Guihenneuc-Jouyaux C, Campanella G, Richardson S, Vermeulen R, De Iorio M, Galea S, Vineis P
Source: Epidemiology, 2014 Jan;25(1), p. 28-34.
PMID: 24240650
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A unified framework integrating parent-of-origin effects for association study.
Authors: Xiao F, Ma J, Amos CI
Source: PLoS One, 2013;8(8), p. e72208.
EPub date: 2013 Aug 26.
PMID: 23991061
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Empirical hierarchical bayes approach to gene-environment interactions: development and application to genome-wide association studies of lung cancer in TRICL.
Authors: Sohns M, Viktorova E, Amos CI, Brennan P, Fehringer G, Gaborieau V, Han Y, Heinrich J, Chang-Claude J, Hung RJ, Müller-Nurasyid M, Risch A, Lewinger JP, Thomas DC, Bickeböller H
Source: Genet Epidemiol, 2013 Sep;37(6), p. 551-9.
EPub date: 2013 Jul 26.
PMID: 23893921
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Mesolimbic dopamine and habenulo-interpeduncular pathways in nicotine withdrawal.
Authors: Dani JA, De Biasi M
Source: Cold Spring Harb Perspect Med, 2013 Jun 1;3(6), p. null.
EPub date: 2013 Jun 1.
PMID: 23732854
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Cytokinesis-blocked micronucleus cytome assay and spectral karyotyping as methods for identifying chromosome damage in a lung cancer case-control population.
Authors: Lloyd SM, Lopez M, El-Zein R
Source: Genes Chromosomes Cancer, 2013 Jul;52(7), p. 694-707.
EPub date: 2013 Apr 30.
PMID: 23630028
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Pilot Study of CYP2B6 Genetic Variation to Explore the Contribution of Nitrosamine Activation to Lung Carcinogenesis.
Authors: Wassenaar CA, Dong Q, Amos CI, Spitz MR, Tyndale RF
Source: Int J Mol Sci, 2013 Apr 16;14(4), p. 8381-92.
EPub date: 2013 Apr 16.
PMID: 23591849
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda KL, Chen GK, Taylor KC, Palmer C, Edwards TL, Lange LA, Ng MC, Adeyemo AA, Allison MA, Bielak LF, Chen G, Graff M, Irvin MR, Rhie SK, Li G, Liu Y, Liu Y, Lu Y, Nalls MA, Sun YV, Wojczynski MK, Yanek LR, Aldrich MC, Ademola A, Amos CI, Bandera EV, Bock CH, Britton A, Broeckel U, Cai Q, Caporaso NE, Carlson CS, Carpten J, Casey G, Chen WM, Chen F, Chen YD, Chiang CW, Coetzee GA, Demerath E, Deming-Halverson SL, Driver RW, Dubbert P, Feitosa MF, Feng Y, Freedman BI, Gillanders EM, Gottesman O, Guo X, Haritunians T, Harris T, Harris CC, Hennis AJ, Hernandez DG, McNeill LH, Howard TD, Howard BV, Howard VJ, Johnson KC, Kang SJ, Keating BJ, Kolb S, Kuller LH, Kutlar A, Langefeld CD, Lettre G, Lohman K, Lotay V, Lyon H, Manson JE, Maixner W, Meng YA, Monroe KR, Morhason-Bello I, Murphy AB, Mychaleckyj JC, Nadukuru R, Nathanson KL, Nayak U, N'diaye A, Nemesure B, Wu SY, Leske MC, Neslund-Dudas C, Neuhouser M, Nyante S, Ochs-Balcom H, Ogunniyi A, Ogundiran TO, Ojengbede O, Olopade OI, Palmer JR, Ruiz-Narvaez EA, Palmer ND, Press MF, Rampersaud E, Rasmussen-Torvik LJ, Rodriguez-Gil JL, Salako B, Schadt EE, Schwartz AG, Shriner DA, Siscovick D, Smith SB, Wassertheil-Smoller S, Speliotes EK, Spitz MR, Sucheston L, Taylor H, Tayo BO, Tucker MA, Van Den Berg DJ, Edwards DR, Wang Z, Wiencke JK, Winkler TW, Witte JS, Wrensch M, Wu X, Yang JJ, Levin AM, Young TR, Zakai NA, Cushman M, Zanetti KA, Zhao JH, Zhao W, Zheng Y, Zhou J, Ziegler RG, Zmuda JM, Fernandes JK, Gilkeson GS, Kamen DL, Hunt KJ, Spruill IJ, Ambrosone CB, Ambs S, Arnett DK, Atwood L, Becker DM, Berndt SI, Bernstein L, Blot WJ, Borecki IB, Bottinger EP, Bowden DW, Burke G, Chanock SJ, Cooper RS, Ding J, Duggan D, Evans MK, Fox C, Garvey WT, Bradfield JP, Hakonarson H, Grant SF, Hsing A, Chu L, Hu JJ, Huo D, Ingles SA, John EM, Jordan JM, Kabagambe EK, Kardia SL, Kittles RA, Goodman PJ, Klein EA, Kolonel LN, Le Marchand L, Liu S, McKnight B, Millikan RC, Mosley TH, Padhukasahasram B, Williams LK, Patel SR, Peters U, Pettaway CA, Peyser PA, Psaty BM, Redline S, Rotimi CN, Rybicki BA, Sale MM, Schreiner PJ, Signorello LB, Singleton AB, Stanford JL, Strom SS, Thun MJ, Vitolins M, Zheng W, Moore JH, Williams SM, Ketkar S, Zhu X, Zonderman AB, NABEC Consortium, UKBEC Consortium, BioBank Japan Project, AGEN Consortium, Kooperberg C, Papanicolaou GJ, Henderson BE, Reiner AP, Hirschhorn JN, Loos RJ, North KE, Haiman CA
Source: Nat Genet, 2013 Jun;45(6), p. 690-6.
EPub date: 2013 Apr 14.
PMID: 23583978
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Role of selected genetic variants in lung cancer risk in African Americans.
Authors: Spitz MR, Amos CI, Land S, Wu X, Dong Q, Wenzlaff AS, Schwartz AG
Source: J Thorac Oncol, 2013 Apr;8(4), p. 391-7.
PMID: 23454887
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Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls.
Authors: Brenner DR, Brennan P, Boffetta P, Amos CI, Spitz MR, Chen C, Goodman G, Heinrich J, Bickeböller H, Rosenberger A, Risch A, Muley T, McLaughlin JR, Benhamou S, Bouchardy C, Lewinger JP, Witte JS, Chen G, Bull S, Hung RJ
Source: Hum Genet, 2013 May;132(5), p. 579-89.
EPub date: 2013 Feb 1.
PMID: 23370545
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Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau.
Authors: Leng S, Picchi MA, Liu Y, Thomas CL, Willis DG, Bernauer AM, Carr TG, Mabel PT, Han Y, Amos CI, Lin Y, Stidley CA, Gilliland FD, Jacobson MR, Belinsky SA
Source: Carcinogenesis, 2013 May;34(5), p. 1044-50.
EPub date: 2013 Jan 25.
PMID: 23354305
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Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.
Authors: Dong J, Jin G, Wu C, Guo H, Zhou B, Lv J, Lu D, Shi Y, Shu Y, Xu L, Chu M, Wang C, Zhang R, Dai J, Jiang Y, Yu D, Ma H, Zhao X, Yin Z, Yang L, Li Z, Deng Q, Cao S, Qin Z, Gong J, Sun C, Wang J, Wu W, Zhou G, Chen H, Guan P, Chen Y, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Liu J, Amos CI, Chen F, Tan W, Jin L, Wu T, Hu Z, Lin D, Shen H
Source: PLoS Genet, 2013;9(1), p. e1003190.
EPub date: 2013 Jan 17.
PMID: 23341777
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