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Carcinogenesis Advance Access originally published online on September 14, 2006
Carcinogenesis 2007 28(3):625-631; doi:10.1093/carcin/bgl177
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© 2006 The Author
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans

Stefano Bonassi1,*, Ariana Znaor3, Marcello Ceppi1, Cecilia Lando1, Wushou Peter Chang4, Nina Holland5, Micheline Kirsch-Volders6, Errol Zeiger7, Sadayuki Ban8,22, Roberto Barale9, Maria Paola Bigatti10, Claudia Bolognesi2, Antonina Cebulska-Wasilewska11, Eleonora Fabianova12, Alexandra Fucic13, Lars Hagmar14,{dagger}, Gordana Joksic15, Antonietta Martelli16, Lucia Migliore9, Ekaterina Mirkova17, Maria Rosaria Scarfi18, Andrea Zijno19, Hannu Norppa20 and Michael Fenech21

1 Unit of Molecular Epidemiology, National Cancer Research Institute Genoa, Italy
2 Unit of Environmental Carcinogenesis, National Cancer Research Institute Genoa, Italy
3 Croatian National Cancer Registry, Croatian National Institute of Public Health Zagreb, Croatia
4 Institute of Environmental Health Sciences, National Yang Ming University Medical School Taipei, Taiwan
5 School of Public Health, University of California Berkeley, CA, USA
6 Laboratory for Cell Genetics, Vrije Universiteit Brussel Brussel, Belgium
7 Errol Zeiger Consulting, Chapel Hill NC, USA
8 Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation Hiroshima, Japan
9 Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa Pisa, Italy
10 Dipartimento di Biologia Animale, University of Turin Turin, Italy
11 Chair of Epidemiology and Preventive Medicine, Jagiellonian University Medical College Kraków, Poland
12 State Health Institute, Banská Bystrica Slovakia
13 Institute for Medical Research and Occupational Health, Zagreb Croatia
14 Department of Occupational and Environmental Medicine, Lund University Lund, Sweden
15 Vinca Institute of Nuclear Sciences, Medical Protection Centre Belgrade, Yugoslavia
16 DIMI, University of Genoa Genoa, Italy
17 National Center of Public Health Protection, Sofia Bulgaria
18 CNR-IREA, Naples Italy
19 Department of Environment and Primary Prevention, Istituto Superiore di Sanità Rome, Italy
20 New Technologies and Risks, Finnish Institute of Occupational Health Helsinki, Finland
21 CSIRO Human Nutrition, Adelaide Australia
22 Present address: National Institute of Radiological Sciences, Chiba Japan

*To whom correspondence should be addressed at: Unit of Molecular Epidemiology, National Cancer Research Institute, Largo R. Benzi, 10, 16132-I, Genoa, Italy. Tel: +390 10 5600 924; Fax: +390 10 5600 501; Email: stefano.bonassi{at}istge.it

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.

Abbreviations: CA, chromosomal aberrations; HUMN, HUman MicroNucleus project; MN, micronucleus; PBL, peripheral blood lymphocytes.

{dagger}We wish to dedicate this study to Dr Lars Hagmar, a good person, a helpful and supportive colleague, and an outstanding scientist, who died on June 14, 2006.

Received July 21, 2006; revised August 30, 2006; accepted September 2, 2006.


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