Carcinogenesis Advance Access published online on September 14, 2006
Carcinogenesis, doi:10.1093/carcin/bgl177
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1 Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy
* To whom correspondence should be addressed. 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 6,718 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.
Received July 21, 2006
Revised August 30, 2006
Accepted September 2, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans
Stefano Bonassi 1 *, Ariana Znaor 2, Marcello Ceppi 1, Cecilia Lando 1, Wushou Peter Chang 3, Nina Holland 4, Micheline Kirsch-Volders 5, Errol Zeiger 6, Sadayuki Ban 7, Roberto Barale 8, Maria Paola Bigatti 9, Claudia Bolognesi 10, Antonina Cebulska-Wasilewska 11, Eleonora Fabianova 12, Alexandra Fucic 13, Lars Hagmar 14 
, Gordana Joksic 15, Antonietta Martelli 16, Lucia Migliore 8, Ekaterina Mirkova 17, Maria Rosaria Scarfi 18, Andrea Zijno 19, Hannu Norppa 20, and Michael Fenech 21
2 Croatian National Cancer Registry, Croatian National Institute of Public Health, Zagreb, Croatia
3 Institute of Environmental Health Sciences, National Yang Ming University Medical School, Taipei, Taiwan
4 School of Public Health, University of California, Berkeley, CA, USA
5 Laboratory for Cell Genetics, Vrije Universiteit Brussel, Brussel, Belgium
6 Errol Zeiger Consulting, Chapel Hill, NC, USA
7 Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan; current address: National Institute of Radiological Sciences, Chiba, Japan
8 Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Pisa, Italy
9 Dipartimento di Biologia Animale, University of Turin, Turin, Italy
10 Unit of Environmental Carcinogenesis, National Cancer Research Institute, Genoa, 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 Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland
21 CSIRO Human Nutrition, Adelaide, Australia
Stefano Bonassi, E-mail: stefano.bonassi{at}istge.it
Abstract 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.
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