TY - JOUR
T1 - An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans
AU - Bonassi, Stefano
AU - Znaor, Ariana
AU - Ceppi, Marcello
AU - Lando, Cecilia
AU - Chang, Wushou Peter
AU - Holland, Nina
AU - Kirsch-Volders, Micheline
AU - Zeiger, Errol
AU - Ban, Sadayuki
AU - Barale, Roberto
AU - Bigatti, Maria Paola
AU - Bolognesi, Claudia
AU - Cebulska-Wasilewska, Antonina
AU - Fabianova, Eleonora
AU - Fucic, Alexandra
AU - Hagmar, Lars
AU - Joksic, Gordana
AU - Martelli, Antonietta
AU - Migliore, Lucia
AU - Mirkova, Ekaterina
AU - Scarfi, Maria Rosaria
AU - Zijno, Andrea
AU - Norppa, Hannu
AU - Fenech, Michael
N1 - Funding Information:
The international collaborative HUMN project was developed to improve knowledge of the biology and relevance of MN induction and its application to human population studies (1). Details about this initiative and the list of publications produced under the HUMN project can be found on the project website, www.HUMN.org. The study was also part of the Cytogenetic Biomarkers and Human Cancer Risk project (CancerRiskBiomarkers), a European collaborative research project funded by the European Union.
Funding Information:
The authors are grateful to Dr Kei Nakachi, Hiroshima, Japan for his constructive comments on the manuscript. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan, under Research Protocols RP10-87 and RP18-61. RERF is a private, non-profit foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the U.S. Department of Energy (DOE), the latter through the U.S. National Academy of Sciences. The authors acknowledge grant support from European Union (Cytogenetic Biomarkers and Human Cancer Risk: QLK4-CT-2000-00628 and QLK4-CT-2002-02831); Associazione Italiana per la Ricerca sul Cancro (AIRC), Italy; Agenzia Spaziale Italiana (ASI), Italy; Lund University. Lund, Sweden; Lund University Hospital, Lund, Sweden and the Finnish Work Environment Fund. Funding to pay the Open Access publication charges for this article was provided by CSIRO Human Nutrition, Food Science Australia.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgl177
DO - 10.1093/carcin/bgl177
M3 - Article
C2 - 16973674
AN - SCOPUS:34047154552
SN - 0143-3334
VL - 28
SP - 625
EP - 631
JO - Carcinogenesis
JF - Carcinogenesis
IS - 3
ER -
