An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans.
Stefano Bonassi,Ariana Znaor,Marcello Ceppi,Cecilia Lando,Wushou P. Chang,Nina Holland,Micheline Kirsch-Volders,Errol Zeiger,Sadayuki Ban,Sadayuki Ban,Roberto Barale,Maria Paola Bigatti,Claudia Bolognesi,Antonina Cebulska-Wasilewska,Eleonora Fabianova,Alexandra Fucic,Lars Hagmar,Gordana Joksić,Antonietta Martelli,Lucia Migliore,Ekaterina Mirkova,Maria Rosaria Scarfì,Andrea Zijno,Hannu Norppa,Michael Fenech +24 more
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TLDR
Preliminary evidence is provided that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects and in all national cohorts and for all major cancer sites.Abstract:
The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR = 1.84; 95% CI: 1.28-2.66) and high MN frequency (RR = 1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P = 0.001 and P = 0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR = 2.80; 1.17-6.73) and gastro-intestinal cancers (RR = 1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.read more
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Cytokinesis-block micronucleus cytome assay
TL;DR: The cytokinesis-block micronucleus cytome assay is a comprehensive system for measuring DNA damage, cytostasis and cytotoxicity and is being applied successfully for biomonitoring of in vivo genotoxin exposure, in vitro genotoxicity testing and in diverse research fields such as nutrigenomics and pharmacogenomics as a predictor of normal tissue and tumor radiation sensitivity and cancer risk.
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The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: The HUMN project perspective on current status and knowledge gaps
Nina Holland,Claudia Bolognesi,Micheline Kirsch-Volders,Stefano Bonassi,Errol Zeiger,Siegfried Knasmueller,Michael Fenech +6 more
TL;DR: The harmonization and standardization of the buccal MN assay will allow more reliable comparison of the data among human populations and laboratories, evaluation of the assay's performance, and consolidation of its world-wide use for biomonitoring of DNA damage.
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Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies
TL;DR: Preliminary evidence that MN frequency in peripheral blood lymphocytes is predictive of cancer risk is provided, suggesting that increased MN formation is associated with early events in carcinogenesis.
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References
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Journal ArticleDOI
Measurement of micronuclei in lymphocytes.
TL;DR: The cytokinesis-block method appears to be the procedure of choice for quantitating micronuclei in lymphocytes and was of no value for measuring pre-existing chromosomal damage present in vivo.
Book
Statistical Models in Epidemiology
David Clayton,Michael Hills +1 more
TL;DR: This self-contained account of the statistical basis of epidemiology has been written specifically for those with a basic training in biology, therefore no previous knowledge is assumed and the mathematics is deliberately kept at a manageable level.
Journal ArticleDOI
HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures.
Michael Fenech,Wushou P. Chang,Micheline Kirsch-Volders,Nina Holland,Stefano Bonassi,Errol Zeiger +5 more
TL;DR: Criteria for scoring micron nuclei and nucleoplasmic bridges in binucleated cells in the cytokinesis-block micronucleus assay for isolated human lymphocyte cultures are described in detail and will assist in the development of a procedure for calibrating scorers and laboratories so that results from different laboratories may be more comparable in the future.
Journal ArticleDOI
On the road to cancer: aneuploidy and the mitotic checkpoint.
TL;DR: Defects in the mitotic checkpoint generate aneuploidy and might facilitate tumorigenesis, but more severe disabling of checkpoint signalling is a possible anticancer strategy.