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Grant Details

Grant Number: 5R01CA098549-05 Interpret this number
Primary Investigator: El-Zein, Randa
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Molecular Biomarkers as Predictors of Hodgkin's Disease
Fiscal Year: 2007
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Abstract

DESCRIPTION (provided by applicant): A major concern for Hodgkin's Disease (HD) survivors is the development of recurrence or second primary tumors. Although factors responsible for the unfavorable outcomes and poor survival of HD patients remain incompletely understood, the population at highest risk seems to be genetically predisposed. In this proposal we propose to evaluate a panel of susceptibility biomarkers as predictors of disease outcome in an existing cohort of 254 HD patients for whom demographic, epidemiological, clinical data and pretreatment blood samples are available. We will test the hypothesis that unfavorable outcomes occur more frequently in patients with poor DNA repair capacity (measures by increase chromosome instability) and with adverse genotypes (polymorphisms in DNA repair and cell cycle control) as compared with patients with favorable outcome. Specifically we propose: 1) To collect follow-up information on health and vital status data to ascertain endpoints (recurrence or second primary tumors) for all the HD patients in the cohort; 2) To phenotypically characterize the role of background chromosomal instability (measured by chromosome aberrations and sister chromatid exchanges) in disease recurrence or development of SPTs. We hypothesize that patients with poor outcomes exhibit higher levels of baseline chromosomal damage than patients with favorable outcome. 3) To elucidate the role that specific polymorphisms in DNA repair capacity genes (XRCC1, XPD and XRCC3) and cell cycle control (p53 gene) play in the modulation of HD outcome. We hypothesize that individuals with DNA repair allelic variants have altered DNA repair capacity and increased risk of developing recurrence or SPT. Similarly, the allelic variants of p53 gene are associated with variant proteins that may alter cell cycle control encouraging progression either by inducing genomic instability and DNA misrepair or by permitting survival of mutants which will in turn have a negative impact on outcome; and 4) To analyze epidemiological and biomarker data independently and jointly as predictors of recurrence and development of SPTs. Identification of subgroups of HD patients who are at increased risk for recurrence or second primary tumor development has both clinical and prognostic relevance. The high risk population can be targeted for intensive preventive and early detection strategies.

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Publications

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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Hodgkin lymphoma risk: role of genetic polymorphisms and gene-gene interactions in DNA repair pathways.
Authors: Monroy C.M. , Cortes A.C. , Lopez M. , Rourke E. , Etzel C.J. , Younes A. , Strom S.S. , El-Zein R. .
Source: Molecular carcinogenesis, 2011 Nov; 50(11), p. 825-34.
EPub date: 2011-03-03.
PMID: 21374732
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Variants in folate pathway genes as modulators of genetic instability and lung cancer risk.
Authors: Piskac-Collier A.L. , Monroy C. , Lopez M.S. , Cortes A. , Etzel C.J. , Greisinger A.J. , Spitz M.R. , El-Zein R.A. .
Source: Genes, chromosomes & cancer, 2011 Jan; 50(1), p. 1-12.
PMID: 20842733
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Rapid method for determination of DNA repair capacity in human peripheral blood lymphocytes amongst smokers.
Authors: El-Zein R.A. , Monroy C.M. , Cortes A. , Spitz M.R. , Greisinger A. , Etzel C.J. .
Source: BMC cancer, 2010-08-18; 10, p. 439.
EPub date: 2010-08-18.
PMID: 20718982
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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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Regulatory regions responsive to oxidative stress in the promoter of the human DNA glycosylase gene NEIL2.
Authors: Kinslow C.J. , El-Zein R.A. , Rondelli C.M. , Hill C.E. , Wickliffe J.K. , Abdel-Rahman S.Z. .
Source: Mutagenesis, 2010 Mar; 25(2), p. 171-7.
EPub date: 2009-11-27.
PMID: 19945985
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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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Single nucleotide polymorphisms 5' upstream the coding region of the NEIL2 gene influence gene transcription levels and alter levels of genetic damage.
Authors: Kinslow C.J. , El-Zein R.A. , Hill C.E. , Wickliffe J.K. , Abdel-Rahman S.Z. .
Source: Genes, chromosomes & cancer, 2008 Nov; 47(11), p. 923-32.
PMID: 18651651
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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
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Human sensitivity to PhIP: a novel marker for prostate cancer risk.
Authors: El-Zein R. , Etzel C.J. , Lopez M.S. , Gu Y. , Spitz M.R. , Strom S.S. .
Source: Mutation research, 2006-10-10; 601(1-2), p. 1-10.
EPub date: 2006-08-04.
PMID: 16889804
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Cytokinesis-blocked micronucleus assay as a novel biomarker for lung cancer risk.
Authors: El-Zein R.A. , Schabath M.B. , Etzel C.J. , Lopez M.S. , Franklin J.D. , Spitz M.R. .
Source: Cancer research, 2006-06-15; 66(12), p. 6449-56.
PMID: 16778224
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Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cells.
Authors: Deng C.Z. , Fons M.P. , Rosenblatt J. , El-Zein R.A. , Abdel-Rahman S.Z. , Albrecht T. .
Source: Environmental and molecular mutagenesis, 2006 Apr; 47(3), p. 150-61.
PMID: 16329104
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Evaluation of two different biomarkers for use in the assessment of toxic chemical exposure in California sea lions (Zalophus californianus).
Authors: El-Zein R.A. , Hastings-Smith D.A. , Ammenheuser M.M. , Treinen-Moslen M. , Gulland F.M. , Ward J.B. .
Source: Marine pollution bulletin, 2006 Jan; 52(1), p. 108-13.
EPub date: 2005-11-18.
PMID: 16298399
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Differential mutagen sensitivity of peripheral blood lymphocytes from smokers and nonsmokers: effect of human cytomegalovirus infection.
Authors: Albrecht T. , Deng C.Z. , Abdel-Rahman S.Z. , Fons M. , Cinciripini P. , El-Zein R.A. .
Source: Environmental and molecular mutagenesis, 2004; 43(3), p. 169-78.
PMID: 15065204
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