Carcinogenesis Advance Access originally published online on March 19, 2008
Carcinogenesis 2008 29(6):1178-1183; 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
1 Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy
2 New Technologies and Risks, Work Environment Development, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FI-00250 Helsinki Finland
3 Department of Occupational and Environmental Medicine, Lund University, S-221 85 Lund, Sweden
4 Environmental and Occupational Health Division, Institute for Risk Assessment Sciences, University Utrecht, Utrecht, PO Box 80176, 3503 TD Utrecht, The Netherlands
5 Croatian National Cancer Registry, Croatian National Institute of Public Health, Rockefellerova 7, 10000 Zagreb, Croatia
6 Department of Radiation and Environmental Biology, The Henryk Niewodniczanski Institute of Nuclear Physics, PAN, Radzikowskiego Street 152, 31-342 Kraków, poland
7 Department of Occupational Health, Specialized State Health Institute, Banska Bystrica, Slovakia
8 Institute for Medical Research and Occupational Health, 10 000 Zagreb, Ksaverska c 2 Croatia
9 Department of Diagnostic Onco-cytogenetics, National Institute of Oncology, Ráth Gy. u. 7-9, Budapest 1122, Hungary
10 Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, Skien, Norway
11 Environmental Health Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, Po Box 2099, 1014 Copenhagen K, Denmark
12 Vilnius University, Universiteto 3, 01513 Vilnius, Lithuania
13 Laboratory of Genetic Ecotoxicology, c/o Institute of Experimental Medicine Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
14 Genetics and Epidemiology Cluster, International Agency for Research on Cancer, 150 cours Albert Thomas, 69008 Lyon, France
* To whom correspondence should be addressed. Tel: +390 10 5600924; Fax: +390 10 5600501; Email: 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 that 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.
Abbreviations: CA, chromosomal aberration; CI, confidence interval; IR, ionizing radiation; RR, relative risk
Received January 18, 2008; revised March 5, 2008; accepted March 6, 2008.