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Grant Details

Grant Number: 3R01CA060691-15S1 Interpret this number
Primary Investigator: Schwartz, Ann
Organization: Wayne State University
Project Title: Genetic Epidemiology of Lung Cancer
Fiscal Year: 2009
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Abstract

Studies of familial aggregation and differences in risk after exposure suggest that genetics plays a role in lung cancer susceptibility. Two studies, including this one, have found evidence consistent with Mendelian codominant inheritance of a rare autosomal gene in lung cancer and one linkage study is underway. Linkage studies in lung cancer are limited by the late age of onset and the rapidly fatal nature of the disease. Inconsistent findings have been reported in studies of candidate susceptibility genes focused on phase I and phase II enzyme polymorphisms and DNA repair enzyme polymorphisms. Overall, these studies have several limitations including a focus on only a small number of polymorphisms, small sample sizes, bias due to population stratification, and variations across populations. An alternative approach to the discovery of genes for complex diseases is through admixture mapping. Recently admixed populations, such as African Americans, provide the most power for this type of analysis. To further characterize genetic risk of lung cancer, the proposed study will use new methodology and a recently validated panel of SNPs in a case-only study design to identify genetic markers for lung cancer in African Americans. The specific aims of the proposed study are: 1) to accrue 800 African American lung cancer cases for admixture mapping; 2) to identify regions showing evidence of linkage to lung cancer susceptibility using admixture mapping methods in 800 cases and 200 controls (used to check model assumptions) using 3,011 SNPs known to differ in frequency by > 0.5 between Africans and European Americans and spaced 1.2cM across the genome; and 3) to continue to extend families with three or more lung cancer affected family members for future linkage studies. This will be the first study to use admixture mapping to identify susceptibility genes for lung cancer. By focusing on the African American population, with demonstrated admixture, this approach can be used successfully and is the next logical step in this research.

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Publications

Frequency and type of epidermal growth factor receptor mutations in African Americans with non-small cell lung cancer.
Authors: Cote ML, Haddad R, Edwards DJ, Atikukke G, Gadgeel S, Soubani AO, Lonardo F, Bepler G, Schwartz AG, Ethier SP
Source: J Thorac Oncol, 2011 Mar;6(3), p. 627-30.
PMID: 21317742
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Admixture mapping of lung cancer in 1812 African-Americans.
Authors: Schwartz AG, Wenzlaff AS, Bock CH, Ruterbusch JJ, Chen W, Cote ML, Artis AS, Van Dyke AL, Land SJ, Harris CC, Pine SR, Spitz MR, Amos CI, Levin AM, McKeigue PM
Source: Carcinogenesis, 2011 Mar;32(3), p. 312-7.
EPub date: 2010 Nov 29.
PMID: 21115650
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Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans.
Authors: Reinersman JM, Johnson ML, Riely GJ, Chitale DA, Nicastri AD, Soff GA, Schwartz AG, Sima CS, Ayalew G, Lau C, Zakowski MF, Rusch VW, Ladanyi M, Kris MG
Source: J Thorac Oncol, 2011 Jan;6(1), p. 28-31.
PMID: 21107288
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Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.
Authors: Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen X, Cichon S, Giegling I, Han S, Han Y, Keskitalo-Vuokko K, Kong X, Landi MT, Ma JZ, Short SE, Stephens SH, Stevens VL, Sun L, Wang Y, Wenzlaff AS, Aggen SH, Breslau N, Broderick P, Chatterjee N, Chen J, Heath AC, Heliövaara M, Hoft NR, Hunter DJ, Jensen MK, Martin NG, Montgomery GW, Niu T, Payne TJ, Peltonen L, Pergadia ML, Rice JP, Sherva R, Spitz MR, Sun J, Wang JC, Weiss RB, Wheeler W, Witt SH, Yang BZ, Caporaso NE, Ehringer MA, Eisen T, Gapstur SM, Gelernter J, Houlston R, Kaprio J, Kendler KS, Kraft P, Leppert MF, Li MD, Madden PA, Nöthen MM, Pillai S, Rietschel M, Rujescu D, Schwartz A, Amos CI, Bierut LJ
Source: PLoS Genet, 2010 Aug 5;6(8), p. null.
EPub date: 2010 Aug 5.
PMID: 20700436
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Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.
Authors: Schwartz AG, Cote ML, Wenzlaff AS, Land S, Amos CI
Source: J Thorac Oncol, 2009 Oct;4(10), p. 1195-201.
PMID: 19641473
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Development and validation of a lung cancer risk prediction model for African-Americans.
Authors: Etzel CJ, Kachroo S, Liu M, D'Amelio A, Dong Q, Cote ML, Wenzlaff AS, Hong WK, Greisinger AJ, Schwartz AG, Spitz MR
Source: Cancer Prev Res (Phila), 2008 Sep;1(4), p. 255-65.
PMID: 19138969
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The molecular epidemiology of lung cancer.
Authors: Schwartz AG, Prysak GM, Bock CH, Cote ML
Source: Carcinogenesis, 2007 Mar;28(3), p. 507-18.
EPub date: 2006 Dec 20.
PMID: 17183062
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Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: a population-based study.
Authors: Cote ML, Wenzlaff AS, Bock CH, Land SJ, Santer SK, Schwartz DR, Schwartz AG
Source: Lung Cancer, 2007 Mar;55(3), p. 255-62.
EPub date: 2006 Dec 15.
PMID: 17174438
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Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex.
Authors: Schwartz AG, Prysak GM, Murphy V, Lonardo F, Pass H, Schwartz J, Brooks S
Source: Clin Cancer Res, 2005 Oct 15;11(20), p. 7280-7.
PMID: 16243798
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Familial lung cancer: genetic susceptibility and relationship to chronic obstructive pulmonary disease.
Authors: Schwartz AG, Ruckdeschel JC
Source: Am J Respir Crit Care Med, 2006 Jan 1;173(1), p. 16-22.
EPub date: 2005 Sep 1.
PMID: 16141445
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CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study.
Authors: Wenzlaff AS, Cote ML, Bock CH, Land SJ, Santer SK, Schwartz DR, Schwartz AG
Source: Carcinogenesis, 2005 Dec;26(12), p. 2207-12.
EPub date: 2005 Jul 28.
PMID: 16051642
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Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer.
Authors: Coté ML, Kardia SL, Wenzlaff AS, Ruckdeschel JC, Schwartz AG
Source: JAMA, 2005 Jun 22;293(24), p. 3036-42.
PMID: 15972566
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Examining population stratification via individual ancestry estimates versus self-reported race.
Authors: Barnholtz-Sloan JS, Chakraborty R, Sellers TA, Schwartz AG
Source: Cancer Epidemiol Biomarkers Prev, 2005 Jun;14(6), p. 1545-51.
PMID: 15941970
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Combinations of glutathione S-transferase genotypes and risk of early-onset lung cancer in Caucasians and African Americans: a population-based study.
Authors: Cote ML, Kardia SL, Wenzlaff AS, Land SJ, Schwartz AG
Source: Carcinogenesis, 2005 Apr;26(4), p. 811-9.
EPub date: 2005 Jan 20.
PMID: 15661806
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Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers.
Authors: Divine KK, Pulling LC, Marron-Terada PG, Liechty KC, Kang T, Schwartz AG, Bocklage TJ, Coons TA, Gilliland FD, Belinsky SA
Source: Int J Cancer, 2005 Apr 10;114(3), p. 400-5.
PMID: 15578700
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GSTM1, GSTT1 and GSTP1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study.
Authors: Wenzlaff AS, Cote ML, Bock CH, Land SJ, Schwartz AG
Source: Carcinogenesis, 2005 Feb;26(2), p. 395-401.
EPub date: 2004 Nov 4.
PMID: 15528218
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NQO1 T allele associated with decreased risk of later age at diagnosis lung cancer among never smokers: results from a population-based study.
Authors: Bock CH, Wenzlaff AS, Cote ML, Land SJ, Schwartz AG
Source: Carcinogenesis, 2005 Feb;26(2), p. 381-6.
EPub date: 2004 Oct 21.
PMID: 15498787
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A major lung cancer susceptibility locus maps to chromosome 6q23-25.
Authors: Bailey-Wilson JE, Amos CI, Pinney SM, Petersen GM, de Andrade M, Wiest JS, Fain P, Schwartz AG, You M, Franklin W, Klein C, Gazdar A, Rothschild H, Mandal D, Coons T, Slusser J, Lee J, Gaba C, Kupert E, Perez A, Zhou X, Zeng D, Liu Q, Zhang Q, Seminara D, Minna J, Anderson MW
Source: Am J Hum Genet, 2004 Sep;75(3), p. 460-74.
EPub date: 2004 Jul 21.
PMID: 15272417
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Lung cancer risk in relatives of early-onset lung cancer cases.
Authors: Cote ML, Spindler AJ, Schwartz AG
Source: Chest, 2004 May;125(5 Suppl), p. 89S-90S.
PMID: 15136431
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Genetic predisposition to lung cancer.
Authors: Schwartz AG
Source: Chest, 2004 May;125(5 Suppl), p. 86S-9S.
PMID: 15136430
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Promoter hypermethylation of the O6-methylguanine-DNA methyltransferase gene: more common in lung adenocarcinomas from never-smokers than smokers and associated with tumor progression.
Authors: Pulling LC, Divine KK, Klinge DM, Gilliland FD, Kang T, Schwartz AG, Bocklage TJ, Belinsky SA
Source: Cancer Res, 2003 Aug 15;63(16), p. 4842-8.
PMID: 12941804
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Familial aggregation of breast cancer with early onset lung cancer.
Authors: Schwartz AG, Siegfried JM, Weiss L
Source: Genet Epidemiol, 1999 Nov;17(4), p. 274-84.
PMID: 10520210
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Lung cancer risk in families of nonsmoking probands: heterogeneity by age at diagnosis.
Authors: Yang P, Schwartz AG, McAllister AE, Swanson GM, Aston CE
Source: Genet Epidemiol, 1999 Nov;17(4), p. 253-73.
PMID: 10520209
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Increased cancer risk among relatives of nonsmoking lung cancer cases.
Authors: Schwartz AG, Rothrock M, Yang P, Swanson GM
Source: Genet Epidemiol, 1999;17(1), p. 1-15.
PMID: 10323181
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Analysis of age of onset data from case-control family studies.
Authors: Li H, Yang P, Schwartz AG
Source: Biometrics, 1998 Sep;54(3), p. 1030-9.
PMID: 9750249
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Genetic analysis of families with nonsmoking lung cancer probands.
Authors: Yang P, Schwartz AG, McAllister AE, Aston CE, Swanson GM
Source: Genet Epidemiol, 1997;14(2), p. 181-97.
PMID: 9129963
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Familial risk of lung cancer among nonsmokers and their relatives.
Authors: Schwartz AG, Yang P, Swanson GM
Source: Am J Epidemiol, 1996 Sep 15;144(6), p. 554-62.
PMID: 8797515
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