| Cytokinesis-blocked micronucleus cytome assay biomarkers identify lung cancer cases amongst smokers. | |
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MedLine Citation:
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PMID: 18483333 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The multi-endpoint cytokinesis-blocked micronucleus assay is used for assessing chromosome aberrations. We have recently reported that this assay is extremely sensitive to genetic damage caused by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and that the binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds in lymphocytes (chromosome damage endpoints measured by the assay) are strong predictors of lung cancer risk. In the current study, we refined our analysis to include toxicity endpoints (micronuclei in mononucleated cells, apoptosis, necrosis, and nuclear division index) to investigate the benefit of including these variables on improving the predictive value of the assay. Baseline and NNK-induced micronuclei in mononucleated cells were significantly higher in patients (n = 139) than controls (n = 130; P < 0.001). Baseline apoptosis was higher among cases; however, the controls showed a significant higher fold increase in NNK-induced apoptosis compared with baseline (P < 0.001). Principal components analysis was used to derive a summary measure for all endpoints and calculate the positive predictive value (PPV) and negative predictive value (NPV) for disease status. First principal component for NNK-induced chromosome damage endpoints (binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds) had an area under the curve = 97.9 (95% confidence interval, 95.9-99.0), PPV = 94.8, and NPV = 92.6. The discriminatory power improved when micronuclei in mononucleated cells were included: area under the curve = 99.1 (95% confidence interval, 97.9-100.0), PPV = 98.7 and NPV = 95.6. The simplicity, rapidity, and sensitivity of the assay together with potential for automation make it a valuable tool for screening and prioritizing potential cases for intensive screening. |
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Authors:
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Randa A El-Zein; Michael Fenech; Mirtha S Lopez; Margaret R Spitz; Carol J Etzel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Volume: 17 ISSN: 1055-9965 ISO Abbreviation: Cancer Epidemiol. Biomarkers Prev. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-05-16 Completed Date: 2008-09-30 Revised Date: 2013-06-05 |
Medline Journal Info:
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Nlm Unique ID: 9200608 Medline TA: Cancer Epidemiol Biomarkers Prev Country: United States |
Other Details:
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Languages: eng Pagination: 1111-9 Citation Subset: IM |
Affiliation:
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Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-1439, USA. relzein@mdanderson.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Case-Control Studies Chi-Square Distribution Chromosome Aberrations Cytokinesis / genetics DNA Damage Female Genetic Predisposition to Disease Humans Logistic Models Lung Neoplasms / genetics* Male Micronuclei, Chromosome-Defective Micronucleus Tests* Middle Aged Nitrosamines / diagnostic use Questionnaires Risk Factors Smoking / adverse effects* Tumor Markers, Biological / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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CA093592/CA/NCI NIH HHS; CA55769/CA/NCI NIH HHS; CA70907/CA/NCI NIH HHS; CA98549/CA/NCI NIH HHS; ES07784/ES/NIEHS NIH HHS; K07 CA093592-05/CA/NCI NIH HHS; R01 CA123208-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nitrosamines; 0/Tumor Markers, Biological; 64091-91-4/4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone |
| Comments/Corrections | |
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