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Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.

Elevated levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes, widely used as a cytogenetic biomarker of genotoxic effects, have been linked to cancer predisposition. However, tobacco smoking, occupational carcinogen exposure, or time since CA analysis do not appear to explain the cancer predictivity of CAs. Alternatively, the observed CA-cancer association could reflect unidentified exposures or individual susceptibility. We assessed the effects of genetic polymorphisms of DNA repair proteins and xenobiotic-metabolizing enzymes (XMEs) on the levels of CAs and sister chromatid exchanges (SCEs) in peripheral lymphocytes of 145 (CAs) and 60 (SCEs) healthy Caucasians. Genotypes of DNA repair genes X-ray repair cross-complementation group 1 (XRCC1 codons 194, 280, 399) and 3 (XRCC3 codon 241 [corrected]), and XME genes glutathione-S-transferase (GST) M1 and T1 and N-acetyl transferase 2 (NAT2) were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP)-based methods. After Poisson regression adjustment for age, sex, smoking, country, and genotypes, a higher frequency of chromosome-type breaks was observed for NAT2 slow acetylators (in nonsmokers) and GSTT1 null subjects (in smokers). Individuals carrying variant alleles for XRCC1 codons 280 and 194 showed a decreased level of chromosome-type breaks. The effect of GSTM1 null and XRCC1 codon 399 genotypes on the frequency of CAs was modified by smoking. In linear regression models adjusting for age, sex, smoking, and genotypes, none of the polymorphisms significantly affected SCE frequency, although GSTT1 null subjects had a slightly elevated SCE level. Our results are in line with earlier findings on the influence of NAT2, GSTT1, and GSTM1 polymorphisms on the level of lymphocyte chromosome damage and suggest that also XRCC1 polymorphism affects CA frequencies, thus apparently influencing DNA repair phenotype. It remains to be examined whether these or other genetic polymorphisms could explain the observed cancer risk predictivity of high CA frequency.

Chromosomal aberrations and sister chromatid exchanges were examined in 45 patients with nonseminomatous testicular cancer at different times after the termination of vinblastine, cisplatin and bleomycin (VPB) therapy and in 22 age-matched healthy men and untreated testicular cancer patients. After 36 months, the frequency of unstable aberrations markedly decreased in peripheral blood lymphocytes of VPB-treated patients, however the persistence of aberrant cells even 75 months after the termination of treatment underlines the necessity of longer follow-up of VPB-treated patients in order to evaluate the relationship between their carcinogen sensitivity and the risk of second malignancies.

This paper reports statistically significant elevations in peripheral blood lymphocyte sister chromatid exchange frequencies in persons occupationally exposed to low levels of ionizing radiation when compared with unexposed persons. Low doses of X or gamma rays administered in vitro also produce significant elevations in sister chromatid exchange frequencies, though the magnitude of the increases is dependent upon culture medium and other factors.

Chromosome aberrations and sister chromatid exchanges were examined in testicular tumor patients treated by 4 cycles of vinblastine, cisplatin and bleomycin adjuvant therapy. The predominant aberrations in cells varied among the patients, and due to interindividual variability no time- or dose-dependent changes were observed in cytogenetic data. There was found an overdispersion of aberrations which might be explained by the effect of bleomycin. Sister chromatid exchange (SCE) frequency was slightly increased and showed also an individual variability in the response to vinblastine, cisplatin and bleomycin (VPB) therapy. No correlation with chromosome aberration rate was found. Further data are required for the real estimation of long-term effects of VPB therapy.

Nowadays all people are exposed to mutagens environmentally, occupationally, therapeutically or due to life style. In order to validate any conclusions concerning a possible effect of some kind of these mutagens to the relevant exposed groups, chromosomal analysis was carried out on a standard population (211 persons) distributed randomly from biological and social points of view and on 163 persons, occupationally exposed to different kinds of mutagens. Analysis proved that the mean frequency of chromosomal aberrations (CA) of control was 0.81% and it was similar before and following the Chernobyl events. Data concerning the CA frequency in people exposed occupationally to low doses of ionizing radiations below the internationally accepted permissible level, showed a 2-6-fold increase of aberrant cells. Occupational exposure to chemical mutagens such as vinyl-chloride and organic solvents like benzene and toluene revealed 2-4 times higher frequency of CAs than the control; however, exposures to organophosphorus insecticides reached a 5-6-fold increase in CAs as well. The sister chromatid exchange (SCE) frequency data were in each exposed group higher than the control values. Neither chromosomal aberration frequencies, nor sister chromatid exchanges differed significantly between smokers and non smokers in control and exposed persons.