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Grant Details

Grant Number: 5R01CA070190-05 Interpret this number
Primary Investigator: Belinsky, Steven
Organization: Lovelace Biomedical & Environmental Res
Project Title: Markers for Lung Carcinogenesis in Bronchial Epithelium
Fiscal Year: 2001
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Abstract

DESCRIPTION: (Adapted from Applicant's Abstract). This is a resubmission of a application reviewed at the October 1996 meeting of the EDC-2 Study Section. A detailed response to the comments by the previous reviewers is included. The application has been considerably revised and re-written. Field cancerization is defined as resulting throughout the respiratory tract because of a broad exposure to carcinogens. Thus, cells throughout the airways will develop genetic abnormalities, regardless of whether they develop malignant change. Important to the overall goals is the postulate that genetic abnormalities in these non-malignant bronchial epithelial cells show a strong association for the development of lung cancer. This will be tested by a hospital-based, case-control study, comparing age, gender and smoking matched (essentially all will be smokers or ex-smokers and all will be men) patients with and without lung cancer. Nonmalignant bronchial epithelial cells will be obtained by bronchoscopy and analyzed by fluorescence in situ hybridization and immunohistochemical techniques in order to determine which among the five alterations most common in lung tumors (expression of p53, loss of chromosome fragments at 9p21, 3p21, 17p13, and trisomy 7) show the strongest correlations with this disease. These results will determine whether genetic alterations detected in nonmalignant bronchial cells are markers for respiratory carcinogenesis (c.f., simply markers of exposure) and help identify genetic alterations that are candidate markers of respiratory carcinogenesis.

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Publications

Implication of a Chromosome 15q15.2 Locus in Regulating UBR1 and Predisposing Smokers to MGMT Methylation in Lung.
Authors: Leng S. , Wu G. , Collins L.B. , Thomas C.L. , Tellez C.S. , Jauregui A.R. , Picchi M.A. , Zhang X. , Juri D.E. , Desai D. , et al. .
Source: Cancer research, 2015-08-01; 75(15), p. 3108-17.
EPub date: 2015-07-16.
PMID: 26183928
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Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer.
Authors: Belinsky S.A. .
Source: Carcinogenesis, 2005 Sep; 26(9), p. 1481-7.
EPub date: 2005-01-20.
PMID: 15661809
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Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers.
Authors: Belinsky S.A. , Palmisano W.A. , Gilliland F.D. , Crooks L.A. , Divine K.K. , Winters S.A. , Grimes M.J. , Harms H.J. , Tellez C.S. , Smith T.M. , et al. .
Source: Cancer research, 2002-04-15; 62(8), p. 2370-7.
PMID: 11956099
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Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum.
Authors: Gilliland F.D. , Harms H.J. , Crowell R.E. , Li Y.F. , Willink R. , Belinsky S.A. .
Source: Cancer research, 2002-04-15; 62(8), p. 2248-52.
PMID: 11956078
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Reduced DNA-dependent protein kinase activity is associated with lung cancer.
Authors: Auckley D.H. , Crowell R.E. , Heaphy E.R. , Stidley C.A. , Lechner J.F. , Gilliland F.D. , Belinsky S.A. .
Source: Carcinogenesis, 2001 May; 22(5), p. 723-7.
PMID: 11323390
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The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung.
Authors: Divine K.K. , Gilliland F.D. , Crowell R.E. , Stidley C.A. , Bocklage T.J. , Cook D.L. , Belinsky S.A. .
Source: Mutation research, 2001-01-05; 461(4), p. 273-8.
PMID: 11104903
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Predicting lung cancer by detecting aberrant promoter methylation in sputum.
Authors: Palmisano W.A. , Divine K.K. , Saccomanno G. , Gilliland F.D. , Baylin S.B. , Herman J.G. , Belinsky S.A. .
Source: Cancer research, 2000-11-01; 60(21), p. 5954-8.
PMID: 11085511
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Frequency of trisomy 20 in nonmalignant bronchial epithelium from lung cancer patients and cancer-free former uranium miners and smokers.
Authors: Neft R.E. , Crowell R.E. , Gilliland F.D. , Murphy M.M. , Lane J.L. , Harms H. , Coons T. , Heaphy E. , Belinsky S.A. , Lechner J.F. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1998 Nov; 7(11), p. 1051-4.
PMID: 9829716
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