The pioneering papers published more than one century ago by Theodor Boveri opened the way to extensive research on the mechanism linking chromosomal abnormalities to the pathogenesis of cancer. As a result of this effort, robust theoretical and empirical evidence correlating cytogenetic damage to early stages of cancer in humans was consolidated, and an increased cancer risk was postulated in healthy subjects with high levels of chromosomal aberrations (CA). The first epidemiological investigation aimed at validating CA as predictor of cancer risk was carried out in the early 1990s. In that report the Nordic Study Group described an 80% increased risk of cancer in healthy subjects with high frequencies of CA. The results of this first study were replicated a few years later in a parallel research initiative carried out in Italy, and the subsequent pooled analysis of these two cohorts published in 1998 contributed to refine the quantitative estimate of the CA/cancer association. A small case-control study nested in a cohort of subjects screened for CA in Taiwan found an increased risk in subjects with high frequency of chromosome-type CA, while in 2001 a significant increase of cancer incidence associated with high levels of CA was described in a new independent cohort of radon exposed workers from the Czech Republic. Despite some common limitations affecting study design, the studies cited above have provided results of great interest both for the understanding of mechanisms of early stages of carcinogenesis, and for their potential implication for cancer prevention. The recent evolution of molecular techniques and the refinement of high throughput techniques have the potential to improve the knowledge about the role of specific sub-types of CA and to provide further insight into the mechanisms. Finally, the most challenging perspective in the field is the passage from research to regulation, with the implementation of preventive policies based on the accumulated knowledge.   

1.
Albertini RJ, Anderson D, Douglas GR, Hagmar L, Hemminki K, Merlo F, Natarajan AT, Norppa H, Shuker DE, Tice R, Waters MD, Aitio A: IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. Mutat Res 463:111–172 (2000).
2.
Bolognesi C, Abbondandolo A, Barale R, Casalone R, Dalpra L, De Ferrari M, Degrassi F, Forni A, Lamberti L, Lando C, Migliore L, Padovani P, Pasquini R, Puntoni R, Sbrana I, Stella M, Bonassi S: Age-related increase of chromosome aberrations, sister-chromatid exchanges and micronuclei in human lymphocytes. Cancer Epidemiol Biomarkers Prev 6:249–256 (1997).
3.
Bonassi S: Combining environmental exposure and genetic effect measurements in health outcome assessment. Mutat Res 428:177–185 (1999).
4.
Bonassi S, Abbondandolo A, Camurri L, Dal Pra L, De Ferrari M, Degrassi F, Forni A, Lamberti L, Lando C, Padovani P, Sbrana I, Vecchio D, Puntoni R: Are chromosome aberrations in circulating lymphocytes predictive of a future cancer onset in humans? Preliminary results of an Italian cohort study. Cancer Genet Cytogenet 79:133–135 (1995a).
5.
Bonassi S, Bolognesi C, Abbondandolo A, Barale R, Bigatti P, Camurri L, Dalpra L, De Ferrari M, Forni A, Lando C, Padovani P, Pasquini R, Stella M, Puntoni R: Influence of sex on cytogenetic endpoints: Evidence from a large human sample and review of the literature. Cancer Epidemiol Biomarkers Prev 4:671–679 (1995b).
6.
Bonassi S, Hagmar L, Strömberg U, Huici Montagud A, Tinnerberg H, Forni A, Heikkilä P, Wanders S, Wilhardt P, Hansteen I-L, Knudsen LE, Norppa H, for the European Study Group on Cytogenetic Biomarkers and Health (ESCH): Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. Cancer Res 60:1619–1625 (2000).
7.
Boveri T: Zur Frage der Entstehung maligner Tumoren (Gustav Fisher, Jena 1914).
8.
Dave BJ, Hopwood VL, Spitz MR, Pathak S: Shared cytogenetic abnormalities in lung tumours and corresponding peripheral blood lymphocytes. Int J Oncol 7:1297–1305 (1995).
9.
Durante M, Bonassi S, George K, Cucinotta FA: Risk estimation based on chromosomal aberrations induced by radiation. Radiat Res 156:662–667 (2001).
10.
Hagmar L, Brøgger A, Hansteen I-L, Heim S, Högsted B, Knudsen L, Lambert B, Linnainmaa K, Mitelman F, Nordenson I, Reuterwall C, Salomaa S, Skerfving S, Sorsa M: Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosomal damage. Cancer Res 54:2919–2922 (1994).
11.
Hagmar L, Bonassi S, Strömberg U, Brøgger A, Knudsen L, Norppa H, Reuterwall C: Chromosomal aberrations in lymphocytes predict human cancer – A report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res 58:4117–4121 (1998).
12.
Hande MP, Azizova TV, Gerad CR, Burak LE, Mitchell CR, Khokhryakov VF, Vasilenko EK, Brenner DJ: Past exposure to densely ionizing radiation leaves a unique permanent signature in the genome. Am J hum Genet 72:1162–1170 (2003).
13.
Liou S-H, Lung J-C, Chen Y-H, Yang T, Hsieh L-L, Chen C-J, Wu T-N: Increased chromosome-type chromosome aberration frequencies as biomarkers of cancer risk in a blackfoot endemic area. Cancer Res 59:1481–1484 (1999).
14.
Maffei F, Cantelli Forti G, Castelli E, Stefanini GF, Mattioli S, Hrelia P: Biomarkers to assess the genetic damage induced by alcohol abuse in human lymphocytes. Mutat Res 514:49–58 (2002).
15.
Maierhofer C, Jentsch I, Lederer G, Fauth C, Speicher MR: Multicolor FISH in two and three dimensions for clastogenic analyses. Mutagenesis 17:523–527 (2002).
16.
Nordic Study Group on the Health Risk of Chromosome Damage: An inter-Nordic prospective study on cytogenetic endpoints and cancer risk. Cancer Genet Cytogenet 45:85–92 (1990a).
17.
Nordic Study Group on the Health Risk of Chromosome Damage: A Nordic data base on somatic chromosome damage in humans. Mutat Res 241:325–337 (1990b).
18.
Norppa H: Cytogenetic biomarkers, in Boffeta P, Rice JM, Bird M, Buffler P (eds): Mechanistic Considerations in the Molecular Epidemiology of Cancer (IARC Sci Publ 157, Lyon 2004, in press).
19.
Nowell P, Hungerford D: A minute chromosome in human granulocytic leukemia. Science 132:1497 (1960).
20.
Perera FP: Molecular epidemiology: On the path to prevention? J natl Cancer Inst 92:601–612 (2000).
21.
Peto J: Cancer epidemiology in the last century and the next decade. Nature 411:390–395 (2001).
22.
Pfeiffer P, Goedecke W, Obe G: Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations. Mutagenesis 15:289–302 (2000).
23.
Richardson C, Jasin M: Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405:697 (2000).
24.
Rowley JD: The critical role of chromosome translocations in human leukemias. A Rev Genet 32:495–519 (1998).
25.
Smerhovsky Z, Landa K, Rössner P, Brabec M, Zudova Z, Hola N, Pokorna Z, Mareckova, Hurychova D: Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations. Environ Health Perspect 109:41–45 (2001).
26.
Smerhovsky Z, Landa K, Rössner P, Juzova D, Brabec M, Zudova Z, Hola N, Zarska H, Nevsimalova E: Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations. Mutat Res 514:165–176 (2002).
27.
Taioli E, Bonassi S: Methodological issues in pooled analysis of biomarker studies. Mutat Res 512:85–92 (2002).
28.
Tinnerberg H, Heikkilä P, Huici-Montagud A, Bernal F, Forni A, Wanders S, Welinder H, Wilhardt P, Strömberg U, Norppa H, Knudsen L, Bonassi S, Hagmar L: Retrospective exposure assessment and quality control in an international multicentre case control study. Ann Occup Hyg 47:37–47 (2003).
29.
Tuimala J, Szekely G, Gundy S, Hirvonen A, Norppa H: Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. Carcinogenesis 6:1003–1008 (2002).
30.
Vilenchik MM, Knudson AG: Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer. Proc natl Acad Sci, USA 100:12871–12876 (2003).
© 2003 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.