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Grant Details

Grant Number: 5R01CA087895-05 Interpret this number
Primary Investigator: Schwartz, Ann
Organization: Wayne State University
Project Title: Adenocarinoma of the Lung in Women
Fiscal Year: 2005
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Abstract

DESCRIPTION: In 1998, 80,000 women in the US were diagnosed with lung cancer and incidence rates, particularly of adenocarcinoma, continue to increase among women. Many pieces of evidence suggest that there are gender differences in susceptibility to tobacco carcinogens. Several studies have shown that DNA adducts, p53 mutations, CYP1A1 expression in the lung, and GSTM1 null genotypes are more frequent in females than in males. Reasons for differential susceptibility by gender might be explained by variations in metabolic enzyme functioning or hormonal differences. Some of the same enzymes involved in the metabolism of carcinogens in tobacco smoke are involved in the metabolism of estrogen. The goals of the proposed study are two-fold. First, we will evaluate the role of tobacco smoke and estrogens in determining risk of adenocarcinoma of the lung among women. Secondly, we will evaluate the role of estrogen receptors and c-erbB-2 in lung tumors to further understand the pathways through which estrogen may be acting in the lung. The specific aims are: 1) To conduct a population-based case-control study of the contribution of tobacco exposure, estrogen use, and reproductive history in determining risk of adenocarcinoma of the lung in women. 716 cases will be identified through the Metropolitan Detroit Cancer Surveillance System of the Karmanos Cancer Institute (a SEER participant). An equal number of controls will be selected through random digit dialing. 2) To determine if genotype at the metabolic enzyme loci CYP1A1, CYP1B1, CYP17, CYP19, GSTM1, GSTP1, COMT, and NQO1 are associated with risk of adenocarcinoma of the lung in women. These enzymes are active in both the metabolism of tobacco smoke carcinogens and the synthesis and metabolism of estrogens. 3) To examine gene-gene and gene-environment interactions, focusing on tobacco and estrogen effects. 4) To determine estrogen receptor status (alpha and beta) and c-erbB-2 levels in the lung tumors of women with adenocarcinoma and evaluate risk associated with tobacco exposure, estrogen use, reproductive history, and genotype at metabolic enzyme loci by tumor characteristics. The proposed study represents a focused approach to defining the contribution of genes and environments in risk of adenocarcinoma of the lung in women. The interview component of the study will provide data about individually measured environmental risk factors. Genotypes have been chosen which impact on biologically effective dose of tobacco carcinogens and estrogens in the lung. The study of tumor characteristics will provide insight into mechanism of action. This large, population-based study should provide clues for important prevention and therapeutic strategies for lung cancer.

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Publications

Survival in women with NSCLC: the role of reproductive history and hormone use.
Authors: Katcoff H, Wenzlaff AS, Schwartz AG
Source: J Thorac Oncol, 2014 Mar;9(3), p. 355-61.
PMID: 24496005
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Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.
Authors: Stephens SH, Hartz SM, Hoft NR, Saccone NL, Corley RC, Hewitt JK, Hopfer CJ, Breslau N, Coon H, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Han Y, Hansel NN, Jiang C, Korhonen T, Lind PA, Liu J, Lyytikäinen LP, Michel M, Shaffer JR, Short SE, Sun J, Teumer A, Thompson JR, Vogelzangs N, Vink JM, Wenzlaff A, Wheeler W, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty TH, Benjamin DJ, Bergen AW, Broms U, Cesarini D, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick D, Foroud T, Furberg H, Giegling I, Gillespie NA, Gu F, Hall AS, Hällfors J, Han S, Hartmann AM, Heikkilä K, Hickie IB, Hottenga JJ, Jousilahti P, Kaakinen M, Kähönen M, Koellinger PD, Kittner S, Konte B, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Murray T, Nauck M, North KE, Paré PD, Pergadia M, Ruczinski I, Salomaa V, Viikari J, Willemsen G, Barnes KC, Boerwinkle E, Boomsma DI, Caporaso N, Edenberg HJ, Francks C, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Johannesson M, Kendler KS, Lehtimäki T, Magnusson PK, Marazita ML, Marchini J, Mitchell BD, Nöthen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Schwartz AG, Shete S, Spitz M, Swan GE, Völzke H, Veijola J, Wei Q, Amos C, Cannon DS, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Weiss RB, Kraft P, Bierut LJ, Ehringer MA
Source: Genet Epidemiol, 2013 Dec;37(8), p. 846-59.
EPub date: 2013 Nov 1.
PMID: 24186853
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The relationship between chronic obstructive pulmonary disease and lung cancer in African American patients.
Authors: Mina N, Soubani AO, Cote ML, Suwan T, Wenzlaff AS, Jhajhria S, Samarah H, Schwartz AG
Source: Clin Lung Cancer, 2012 Mar;13(2), p. 149-56.
EPub date: 2011 Nov 29.
PMID: 22129972
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The landscape of recombination in African Americans.
Authors: Hinch AG, Tandon A, Patterson N, Song Y, Rohland N, Palmer CD, Chen GK, Wang K, Buxbaum SG, Akylbekova EL, Aldrich MC, Ambrosone CB, Amos C, Bandera EV, Berndt SI, Bernstein L, Blot WJ, Bock CH, Boerwinkle E, Cai Q, Caporaso N, Casey G, Cupples LA, Deming SL, Diver WR, Divers J, Fornage M, Gillanders EM, Glessner J, Harris CC, Hu JJ, Ingles SA, Isaacs W, John EM, Kao WH, Keating B, Kittles RA, Kolonel LN, Larkin E, Le Marchand L, McNeill LH, Millikan RC, Murphy A, Musani S, Neslund-Dudas C, Nyante S, Papanicolaou GJ, Press MF, Psaty BM, Reiner AP, Rich SS, Rodriguez-Gil JL, Rotter JI, Rybicki BA, Schwartz AG, Signorello LB, Spitz M, Strom SS, Thun MJ, Tucker MA, Wang Z, Wiencke JK, Witte JS, Wrensch M, Wu X, Yamamura Y, Zanetti KA, Zheng W, Ziegler RG, Zhu X, Redline S, Hirschhorn JN, Henderson BE, Taylor HA Jr, Price AL, Hakonarson H, Chanock SJ, Haiman CA, Wilson JG, Reich D, Myers SR
Source: Nature, 2011 Jul 20;476(7359), p. 170-5.
EPub date: 2011 Jul 20.
PMID: 21775986
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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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Cytokine and cytokine receptor single-nucleotide polymorphisms predict risk for non-small cell lung cancer among women.
Authors: Van Dyke AL, Cote ML, Wenzlaff AS, Chen W, Abrams J, Land S, Giroux CN, Schwartz AG
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jun;18(6), p. 1829-40.
PMID: 19505916
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Chronic obstructive lung diseases and risk of non-small cell lung cancer in women.
Authors: Schwartz AG, Cote ML, Wenzlaff AS, Van Dyke A, Chen W, Ruckdeschel JC, Gadgeel S, Soubani AO
Source: J Thorac Oncol, 2009 Mar;4(3), p. 291-9.
PMID: 19190518
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Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women.
Authors: Cote ML, Yoo W, Wenzlaff AS, Prysak GM, Santer SK, Claeys GB, Van Dyke AL, Land SJ, Schwartz AG
Source: Carcinogenesis, 2009 Apr;30(4), p. 626-35.
EPub date: 2009 Jan 27.
PMID: 19174490
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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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COX-2/EGFR expression and survival among women with adenocarcinoma of the lung.
Authors: Van Dyke AL, Cote ML, Prysak GM, Claeys GB, Wenzlaff AS, Murphy VC, Lonardo F, Schwartz AG
Source: Carcinogenesis, 2008 Sep;29(9), p. 1781-7.
EPub date: 2008 May 2.
PMID: 18453539
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Reproductive factors, hormone use, estrogen receptor expression and risk of non small-cell lung cancer in women.
Authors: Schwartz AG, Wenzlaff AS, Prysak GM, Murphy V, Cote ML, Brooks SC, Skafar DF, Lonardo F
Source: J Clin Oncol, 2007 Dec 20;25(36), p. 5785-92.
PMID: 18089876
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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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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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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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