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Grant Details

Grant Number: 5R01CA074386-11 Interpret this number
Primary Investigator: Christiani, David
Organization: Harvard School Of Public Health
Project Title: Genetic Susceptibility to Lung Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): Lung cancer is the most common cause of cancer mortality among both men and women in the United States. Although up to 90 percent of lung cancer is attributable to cigarette smoking, only 10-20 percent of smokers develop bronchogenic carcinoma over their lifetimes. This observation, along with substantial literature implicating heritable polymorphic factors, indicates that other environmental and host factors influence individual susceptibility to tobacco smoke. This proposal will take advantage of recent advances in molecular epidemiology in this competing continuation (R01 CA 74386) by expanding our original aims of evaluating six xenobiotic metabolic polymorphisms in lung cancer to include the assessment of more recently described polymorphic genes that control oxidative metabolism (Phase I) and the conjugation of reactive intermediates (Phase II). In addition, a number of other polymorphic genes that affect lung inflammatory processes, DNA repair, growth factor function, and tumor suppression (oncogenes) will be evaluated, as there is accumulating evidence supporting the role of these non-metabolism polymorphic alleles in lung cancer development. Moreover, this proposal addresses the role of smoking, diet, and genetic factors as effect modifiers for the association between polymorphisms and lung cancer risk, and the potential roles of age and gender in these associations. To assess these gene-environment and gene gene associations in this expanded group of polymorphic genes, our proposal will build on our productive R01 by increasing our sample size and including greater population diversity by increasing minority recruitment. A better understanding of these risks will lead to improved preventive strategies. The proposal directly addresses two "Extraordinary Opportunities" of the National Cancer Institute, specifically the aim to identify genetic variations that affect cancer risk in concert with environmental factors, and research on tobacco-related concerns.

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Publications

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).
Authors: Kim CH, Lee YC, Hung RJ, McNallan SR, Cote ML, Lim WY, Chang SC, Kim JH, Ugolini D, Chen Y, Liloglou T, Andrew AS, Onega T, Duell EJ, Field JK, Lazarus P, Le Marchand L, Neri M, Vineis P, Kiyohara C, Hong YC, Morgenstern H, Matsuo K, Tajima K, Christiani DC, McLaughlin JR, Bencko V, Holcatova I, Boffetta P, Brennan P, Fabianova E, Foretova L, Janout V, Lissowska J, Mates D, Rudnai P, Szeszenia-Dabrowska N, Mukeria A, Zaridze D, Seow A, Schwartz AG, Yang P, Zhang ZF
Source: Int J Cancer, 2014 Oct 15;135(8), p. 1918-30.
EPub date: 2014 Mar 25.
PMID: 24615328
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Smoking and smoking cessation in relation to the development of co-existing non-small cell lung cancer with chronic obstructive pulmonary disease.
Authors: Zhai R, Yu X, Wei Y, Su L, Christiani DC
Source: Int J Cancer, 2014 Feb 15;134(4), p. 961-70.
EPub date: 2013 Aug 29.
PMID: 23921845
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Predictive accuracy of the Liverpool Lung Project risk model for stratifying patients for computed tomography screening for lung cancer: a case-control and cohort validation study.
Authors: Raji OY, Duffy SW, Agbaje OF, Baker SG, Christiani DC, Cassidy A, Field JK
Source: Ann Intern Med, 2012 Aug 21;157(4), p. 242-50.
PMID: 22910935
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Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: a case-only study.
Authors: Zhai R, Zhao Y, Liu G, Ter-Minassian M, Wu IC, Wang Z, Su L, Asomaning K, Chen F, Kulke MH, Lin X, Heist RS, Wain JC, Christiani DC
Source: Cancer, 2012 Feb 1;118(3), p. 804-11.
EPub date: 2011 Jul 12.
PMID: 21751195
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Reduced lung cancer mortality and exposure to synthetic fluids and biocide in the auto manufacturing industry.
Authors: Mehta AJ, Malloy EJ, Applebaum KM, Schwartz J, Christiani DC, Eisen EA
Source: Scand J Work Environ Health, 2010 Nov;36(6), p. 499-508.
EPub date: 2010 Sep 13.
PMID: 20835688
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Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk.
Authors: Zhai R, Liu G, Asomaning K, Su L, Kulke MH, Heist RS, Nishioka NS, Lynch TJ, Wain JC, Lin X, Christiani DC
Source: Carcinogenesis, 2008 Dec;29(12), p. 2330-4.
EPub date: 2008 Sep 9.
PMID: 18780893
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Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer.
Authors: Zhai R, Liu G, Zhou W, Su L, Heist RS, Lynch TJ, Wain JC, Asomaning K, Lin X, Christiani DC
Source: Clin Cancer Res, 2008 Jan 15;14(2), p. 612-7.
PMID: 18223238
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Second hand smoke, age of exposure and lung cancer risk.
Authors: Asomaning K, Miller DP, Liu G, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Lung Cancer, 2008 Jul;61(1), p. 13-20.
EPub date: 2008 Jan 8.
PMID: 18191495
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Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.
Authors: Liu G, Gurubhagavatula S, Zhou W, Wang Z, Yeap BY, Asomaning K, Su L, Heist R, Lynch TJ, Christiani DC
Source: Pharmacogenomics J, 2008 Apr;8(2), p. 129-38.
EPub date: 2007 Mar 20.
PMID: 17375033
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XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk.
Authors: Liu G, Zhou W, Yeap BY, Su L, Wain JC, Poneros JM, Nishioka NS, Lynch TJ, Christiani DC
Source: Carcinogenesis, 2007 Jun;28(6), p. 1254-8.
EPub date: 2007 Jan 29.
PMID: 17264068
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Rectal cancer and exposure to metalworking fluids in the automobile manufacturing industry.
Authors: Malloy EJ, Miller KL, Eisen EA
Source: Occup Environ Med, 2007 Apr;64(4), p. 244-9.
EPub date: 2006 Aug 15.
PMID: 16912088
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Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer.
Authors: Su L, Zhou W, Asomaning K, Lin X, Wain JC, Lynch TJ, Liu G, Christiani DC
Source: Carcinogenesis, 2006 May;27(5), p. 1024-9.
EPub date: 2005 Nov 25.
PMID: 16311244
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Dietary iron, zinc, and calcium and the risk of lung cancer.
Authors: Zhou W, Park S, Liu G, Miller DP, Wang LI, Pothier L, Wain JC, Lynch TJ, Giovannucci E, Christiani DC
Source: Epidemiology, 2005 Nov;16(6), p. 772-9.
PMID: 16222167
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Modeling lung cancer risk in case-control studies using a new dose metric of smoking.
Authors: Thurston SW, Liu G, Miller DP, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2005 Oct;14(10), p. 2296-302.
PMID: 16214908
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Molecular epidemiology of non-small cell lung cancer.
Authors: Liu G, Zhou W, Christiani DC
Source: Semin Respir Crit Care Med, 2005 Jun;26(3), p. 265-72.
PMID: 16052427
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Matrix metalloproteinase-1 promoter polymorphism and lung cancer risk.
Authors: Su L, Zhou W, Park S, Wain JC, Lynch TJ, Liu G, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2005 Mar;14(3), p. 567-70.
PMID: 15767330
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Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer.
Authors: Zhou W, Liu G, Park S, Wang Z, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2005 Feb;14(2), p. 491-6.
PMID: 15734977
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The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms.
Authors: Liu G, Zhou W, Park S, Wang LI, Miller DP, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Cancer, 2004 Dec 15;101(12), p. 2802-8.
PMID: 15534883
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Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.
Authors: Zhou W, Gurubhagavatula S, Liu G, Park S, Neuberg DS, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Clin Cancer Res, 2004 Aug 1;10(15), p. 4939-43.
PMID: 15297394
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On the use of biomarkers for environmental health research.
Authors: Ryan L, Huang W, Thurston SW, Kelsey KT, Wiencke JK, Christiani DC
Source: Stat Methods Med Res, 2004 Jun;13(3), p. 207-25.
PMID: 15198487
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XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy.
Authors: Gurubhagavatula S, Liu G, Park S, Zhou W, Su L, Wain JC, Lynch TJ, Neuberg DS, Christiani DC
Source: J Clin Oncol, 2004 Jul 1;22(13), p. 2594-601.
EPub date: 2004 Jun 1.
PMID: 15173214
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Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk.
Authors: Zhou W, Liu G, Miller DP, Thurston SW, Xu LL, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2003 Apr;12(4), p. 359-65.
PMID: 12692111
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No association between the p21 codon 31 serine-arginine polymorphism and lung cancer risk.
Authors: Su L, Liu G, Zhou W, Xu LL, Miller DP, Park S, Lynch TJ, Wain JC, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2003 Feb;12(2), p. 174-5.
PMID: 12582031
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Counterpoint: the myeloperoxidase -463G-->a polymorphism does not decrease lung cancer susceptibility in Caucasians.
Authors: Xu LL, Liu G, Miller DP, Zhou W, Lynch TJ, Wain JC, Su L, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2002 Dec;11(12), p. 1555-9.
PMID: 12496043
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Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers' pneumoconiosis.
Authors: Zhai R, Liu G, Ge X, Yang C, Huang C, Wu C, Christiani DC
Source: J Occup Environ Med, 2002 Apr;44(4), p. 372-7.
PMID: 11977425
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Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer.
Authors: Zhou W, Liu G, Miller DP, Thurston SW, Xu LL, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Cancer Res, 2002 Mar 1;62(5), p. 1377-81.
PMID: 11888908
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The G to C polymorphism at -174 of the interleukin-6 gene is rare in a Southern Chinese population.
Authors: Zhai R, Liu G, Yang C, Huang C, Wu C, Christiani DC
Source: Pharmacogenetics, 2001 Nov;11(8), p. 699-701.
PMID: 11692078
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The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer.
Authors: Zhou W, Thurston SW, Liu G, Xu LL, Miller DP, Wain JC, Lynch TJ, Su L, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2001 May;10(5), p. 461-6.
PMID: 11352855
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The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer: differential susceptibility based on smoking behavior.
Authors: Xu LL, Wain JC, Miller DP, Thurston SW, Su L, Lynch TJ, Christiani DC
Source: Cancer Epidemiol Biomarkers Prev, 2001 Apr;10(4), p. 303-9.
PMID: 11319169
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