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

Stefano Bonassi, Ariana Znaor, Marcello Ceppi, Cecilia Lando, Wushou Peter Chang, Nina Holland, Micheline Kirsch-Volders, Errol Zeiger, Sadayuki Ban, Roberto Barale, Maria Paola Bigatti, Claudia Bolognesi, Antonina Cebulska-Wasilewska, Eleonora Fabianova, Alexandra Fucic, Lars Hagmar, Gordana Joksic, Antonietta Martelli, Lucia Migliore, Ekaterina MirkovaMaria Rosaria Scarfi, Andrea Zijno, Hannu Norppa, Michael Fenech

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)625-631
Number of pages7
JournalCarcinogenesis
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

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Lymphocytes
Neoplasms
Tumor Biomarkers
Intestinal Neoplasms
Micronucleus Tests
Chromosomal Instability
Genomic Instability
Incidence
Cytogenetics
Population
Healthy Volunteers
Cohort Studies
Biomarkers
Databases
Prospective Studies
Survival
Mortality

ASJC Scopus subject areas

  • Cancer Research

Cite this

Bonassi, S., Znaor, A., Ceppi, M., Lando, C., Chang, W. P., Holland, N., ... Fenech, M. (2007). An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis, 28(3), 625-631. https://doi.org/10.1093/carcin/bgl177

An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. / Bonassi, Stefano; Znaor, Ariana; Ceppi, Marcello; Lando, Cecilia; Chang, Wushou Peter; Holland, Nina; Kirsch-Volders, Micheline; Zeiger, Errol; Ban, Sadayuki; Barale, Roberto; Bigatti, Maria Paola; Bolognesi, Claudia; Cebulska-Wasilewska, Antonina; Fabianova, Eleonora; Fucic, Alexandra; Hagmar, Lars; Joksic, Gordana; Martelli, Antonietta; Migliore, Lucia; Mirkova, Ekaterina; Scarfi, Maria Rosaria; Zijno, Andrea; Norppa, Hannu; Fenech, Michael.

In: Carcinogenesis, Vol. 28, No. 3, 03.2007, p. 625-631.

Research output: Contribution to journalArticle

Bonassi, S, Znaor, A, Ceppi, M, Lando, C, Chang, WP, Holland, N, Kirsch-Volders, M, Zeiger, E, Ban, S, Barale, R, Bigatti, MP, Bolognesi, C, Cebulska-Wasilewska, A, Fabianova, E, Fucic, A, Hagmar, L, Joksic, G, Martelli, A, Migliore, L, Mirkova, E, Scarfi, MR, Zijno, A, Norppa, H & Fenech, M 2007, 'An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans', Carcinogenesis, vol. 28, no. 3, pp. 625-631. https://doi.org/10.1093/carcin/bgl177
Bonassi, Stefano ; Znaor, Ariana ; Ceppi, Marcello ; Lando, Cecilia ; Chang, Wushou Peter ; Holland, Nina ; Kirsch-Volders, Micheline ; Zeiger, Errol ; Ban, Sadayuki ; Barale, Roberto ; Bigatti, Maria Paola ; Bolognesi, Claudia ; Cebulska-Wasilewska, Antonina ; Fabianova, Eleonora ; Fucic, Alexandra ; Hagmar, Lars ; Joksic, Gordana ; Martelli, Antonietta ; Migliore, Lucia ; Mirkova, Ekaterina ; Scarfi, Maria Rosaria ; Zijno, Andrea ; Norppa, Hannu ; Fenech, Michael. / An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. In: Carcinogenesis. 2007 ; Vol. 28, No. 3. pp. 625-631.
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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.",
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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

PY - 2007/3

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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.

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