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Carcinogenesis Advance Access published online on March 19, 2008
Carcinogenesis, doi:10.1093/carcin/bgn075
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Chromosomal Aberration Frequency in Lymphocytes Predicts the Risk of Cancer: Results from a Pooled Cohort Study of 22,358 Subjects in 11 Countries

Stefano Bonassi1, Hannu Norppa2, Marcello Ceppi1, Ulf Stromberg3, Roel Vermeulen4, Ariana Znaor5, Antonina Cebulska-Wasilewska6, Eleonora Fabianova7, Alexandra Fucic8, Sarolta Gundy9, Inger-Lise Hansteen10, Lisbeth E. Knudsen11, Juozas Lazutka12, Pavel Rossner13, Radim J. Sram13 and Paolo Boffetta14

1 Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy
2 Finnish Institute of Occupational Health, Helsinki, Finland
3 Department of Occupational and Environmental Medicine, Lund University, Lund, Sweden
4 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands
5 Croatian National Cancer Registry, Croatian National Institute of Public Health, Zagreb, Croatia
6 H. Niewodniczánski Institute of Nuclear Physics PAN, Kraków, Poland
7 Department of Occupational Health, Specialized State Health Institute, Banska Bystrica, Slovakia
8 Institute for Medical Research and Occupational Health, Zagreb, Croatia
9 National Institute of Oncology, Budapest, Hungary
10 Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, Skien, Norway
11 Environmental Health Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
12 Vilnius University, Vilnius, Lithuania
13 Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Prague, Czech Republic
14 International Agency for Research on Cancer, Lyon, France

Correspondence: Stefano Bonassi, PhD, Unit of Molecular Epidemiology, National Cancer Research Institute, Largo Rosanna Benzi, 10, 16132 Genoa, Italy. Tel. +390-10-5600924, Fax +390-10-5600501 (e-mail: stefano.bonassi{at}istge.it).

Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies which associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22,358 cancer free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965–2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium (RR = 1.31; 95% confidence interval (CI) 1.07–1.60) and in the high (RR = 1.41; 95% CI 1.16–1.72) tertiles, when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI= 1.34-3.68). The strongest association was found for stomach cancer (RRmedium=1.17 (95% CI= 0.37-3.70); RRhigh=3.13 (95% CI= 1.17-8.39)). Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.

Received January 18, 2008; revised March 5, 2008; accepted March 6, 2008.


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