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Grant Details

Grant Number: 5R01CA123208-04 Interpret this number
Primary Investigator: Etzel, Carol
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Chromosomal Aberrations and Risk for Familial Lung Cancer
Fiscal Year: 2009


Abstract

DESCRIPTION (provided by applicant): This proposed study will build upon the extensive epidemiologic database and specimen repository derived from an ongoing lung cancer case/control study "Ecogenetics Study of Lung Cancer" (R01 CA55679, PI: M. Spitz) designed to identify inter-individual differences in susceptibility to tobacco-induced lung carcinogenesis. Recent evidence has suggested that 1) sensitivity to benzo[a]pyrene diol epoxide (BPDE), the metabolic product of benzo[a]pyrene (B[a]P), constituent of tobacco smoke, is a constitutional phenomenon and is a risk predictor for lung cancer; 2) 3p deletion, a common chromosome defect in lung cancer, occurs more frequently in lung tumor tissues of smoking than nonsmoking patients; 3) elevated levels of in vitro BPDE-induced chromosomal damages in peripheral blood lymphocytes (PBLs) at 3p21.3 and 3p21 are associated with risk of lung and other smoking-related cancers; and 4) a novel genetic locus on chromosome 6q 23-25 predisposes increased risk for lung cancer in families with multiple relatives affected with lung cancer. Therefore we propose to extend these findings using the detailed family history data and stored cell suspensions from the parent grant to further elucidation of the molecular targets of BPDE as lung cancer susceptibility loci. We will identify 400 lung cancer patients (200 cases with a positive family history for lung cancer in at least one first degree relative and 200 sporadic cases with no family history of lung cancer) and 200 controls (matched to the sporadic lung cancer cases on sex, age (+/-5 years), smoking, ethnicity and date of enrollment (+/-2 months). Specifically we propose: 1). To determine, using fluorescent in situ hybridization (FISH) techniques, whether BPDE-induced chromosomal aberrations on 3p21.3, 6q23-25 and 9p21 are more common in the cultured peripheral blood lymphocytes (PBLs) of lung cancer patients than controls. Outworking hypothesis is that exposure to in vitro BPDE may preferentially target specific loci and that lung cancer cases will exhibit higher numbers of aberrations than controls. 2). To determine whether BPDE-induced chromosomal aberrations on 3p21.3, 6q23-25 and 9p21 are more common in the lymphocytes (PBLs) of cases with familial lung cancer compared to sporadic lung cancer cases. Our working hypothesis is that aberrations in PBLs are associated with inherited susceptibility and in turn associated with familial lung cancer. 3). To assess the associations between the higher levels of induced aberrations and age, sex, and known environmental and occupational exposures by integrating epidemiologic data with the molecular cytogenetic data. Our hypothesis is that higher levels of BPDE-induced 3p21.3, 6q23-25 and 9p21 aberrations in PBLs are attributed to global genetic instability and their effect on lung cancer risk is independent of other exposures. These data are being routinely collected in the parent grant. These proposed susceptibility markers may be useful as biomarkers to identify high-risk populations that could then be targeted for intensive smoking-cessation programs and could be enrolled into chemoprevention screening trials.



Publications

Self-reported prior lung diseases as risk factors for non-small cell lung cancer in Mexican Americans.
Authors: McHugh M.K. , Schabath M.B. , Ho C.H. , Liu M. , D'Amelio A.M. , Greisinger A.J. , Delclos G.L. , Spitz M.R. , Etzel C.J. .
Source: Journal of immigrant and minority health, 2013 Oct; 15(5), p. 910-7.
PMID: 22847640
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Use of the cytokinesis-blocked micronucleus assay to detect gender differences and genetic instability in a lung cancer case-control study.
Authors: McHugh M.K. , Lopez M.S. , Ho C.H. , Spitz M.R. , Etzel C.J. , El-Zein R.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013 Jan; 22(1), p. 135-45.
EPub date: 2012-11-29.
PMID: 23195992
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Using haplotype analysis to elucidate significant associations between genes and Hodgkin lymphoma.
Authors: D'Amelio A.M. , Monroy C. , El-Zein R. , Etzel C.J. .
Source: Leukemia research, 2012 Nov; 36(11), p. 1359-64.
EPub date: 2012-08-14.
PMID: 22902050
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Assessing environmental and occupational risk factors for lung cancer in Mexican-Americans.
Authors: McHugh M.K. , Kachroo S. , Liu M. , D'Amelio A.M. , Dong Q. , Hong W.K. , Greisinger A.J. , Spitz M.R. , Etzel C.J. .
Source: Cancer causes & control : CCC, 2010 Dec; 21(12), p. 2157-64.
EPub date: 2010-08-31.
PMID: 20809339
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Familial aggregation of glioma: a pooled analysis.
Authors: Scheurer M.E. , Etzel C.J. , Liu M. , Barnholtz-Sloan J. , Wiklund F. , Tavelin B. , Wrensch M.R. , Melin B.S. , Bondy M.L. , GLIOGENE Consortium .
Source: American journal of epidemiology, 2010-11-15; 172(10), p. 1099-107.
EPub date: 2010-09-21.
PMID: 20858744
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Genetically abnormal circulating cells in lung cancer patients: an antigen-independent fluorescence in situ hybridization-based case-control study.
Authors: Katz R.L. , He W. , Khanna A. , Fernandez R.L. , Zaidi T.M. , Krebs M. , Caraway N.P. , Zhang H.Z. , Jiang F. , Spitz M.R. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2010-08-01; 16(15), p. 3976-87.
EPub date: 2010-07-22.
PMID: 20651054
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Comparison of discriminatory power and accuracy of three lung cancer risk models.
Authors: D'Amelio A.M. , Cassidy A. , Asomaning K. , Raji O.Y. , Duffy S.W. , Field J.K. , Spitz M.R. , Christiani D. , Etzel C.J. .
Source: British journal of cancer, 2010-07-27; 103(3), p. 423-9.
EPub date: 2010-06-29.
PMID: 20588271
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A comprehensive haplotype analysis of the XPC genomic sequence reveals a cluster of genetic variants associated with sensitivity to tobacco-smoke mutagens.
Authors: Rondelli C.M. , El-Zein R.A. , Wickliffe J.K. , Etzel C.J. , Abdel-Rahman S.Z. .
Source: Toxicological sciences : an official journal of the Society of Toxicology, 2010 May; 115(1), p. 41-50.
EPub date: 2010-01-27.
PMID: 20106949
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Pooling dietary data using questionnaires with open-ended and predefined responses: implications for comparing mean intake or estimating odds ratios.
Authors: Swartz M.D. , Forman M.R. , Mahabir S. , Etzel C.J. .
Source: American journal of epidemiology, 2010-03-15; 171(6), p. 682-90.
EPub date: 2010-02-05.
PMID: 20139126
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Re: Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk.
Authors: Spitz M.R. , Amos C.I. , D'Amelio A. , Dong Q. , Etzel C. .
Source: Journal of the National Cancer Institute, 2009-12-16; 101(24), p. 1731-2; author reply 1732.
PMID: 19903803
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Maternal current smoking: concordance between adolescent proxy and mother's self-report.
Authors: Vasudevan V. , Etzel C.J. , Spitz M.R. , Wilkinson A.V. .
Source: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2009 Aug; 11(8), p. 1016-9.
EPub date: 2009-06-16.
PMID: 19531668
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Genetic polymorphisms in DNA repair genes as modulators of Hodgkin disease risk.
Authors: El-Zein R. , Monroy C.M. , Etzel C.J. , Cortes A.C. , Xing Y. , Collier A.L. , Strom S.S. .
Source: Cancer, 2009-04-15; 115(8), p. 1651-9.
PMID: 19280628
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Decreasing the cancer burden in developing countries: concerns and recommendations.
Authors: Kachroo S. , Etzel C.J. .
Source: European journal of cancer care, 2009 Jan; 18(1), p. 18-21.
PMID: 19473221
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Development and validation of a lung cancer risk prediction model for African-Americans.
Authors: Etzel C.J. , Kachroo S. , Liu M. , D'Amelio A. , Dong Q. , Cote M.L. , Wenzlaff A.S. , Hong W.K. , Greisinger A.J. , Schwartz A.G. , et al. .
Source: Cancer prevention research (Philadelphia, Pa.), 2008 Sep; 1(4), p. 255-65.
PMID: 19138969
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An expanded risk prediction model for lung cancer.
Authors: Spitz M.R. , Etzel C.J. , Dong Q. , Amos C.I. , Wei Q. , Wu X. , Hong W.K. .
Source: Cancer prevention research (Philadelphia, Pa.), 2008 Sep; 1(4), p. 250-4.
PMID: 19138968
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Cytokinesis-blocked micronucleus cytome assay biomarkers identify lung cancer cases amongst smokers.
Authors: El-Zein R.A. , Fenech M. , Lopez M.S. , Spitz M.R. , Etzel C.J. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 May; 17(5), p. 1111-9.
PMID: 18483333
Related Citations

Trends in prevalence of prognostic factors and survival in lung cancer patients from 1985 to 2004 at a tertiary care center.
Authors: Kachroo S. , Tong L. , Spitz M.R. , Xing Y. , Merriman K. , Zhu D.K. , Fueger J. , Amos C.I. , Etzel C.J. .
Source: Cancer detection and prevention, 2008; 32(2), p. 101-8.
EPub date: 2008-07-17.
PMID: 18639390
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