Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

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

Occupational Exposure to PAHs Influence on Susceptibility to the X-ray Induced DNA Damage and Repair Capacity

Frequently nowadays present in ambient air the polycyclic aromatic hydrocarbons (PAHs) are considered as potential human carcinogens. The aim of our study was to investigate whether occupational exposure to environmental PAHs may affect cellular susceptibility to the induction of DNA damage and its repair efficacy. In this study, performed in Prague (Czech Republic), in two seasonal samplings (~ 100 subjects in each sampling) lymphocytes, isolated from the whole blood samples collected from two groups of subjects, traffic policemen exposed to PAHs and from control, were examined for cellular capacities. The challenging dose (2Gy) of X-rays was applied as DNA strands breaks. An alkaline version of Single Cell Gel Electrophoresis (SCGE) assay was used to study DNA damage in the cells before challenging treatment, immediately after exposure and after the incubation allowing the cells to complete the fast repair process. In each in vitro experiment, lymphocytes from the same pool of healthy male donors cells served as an internal standard. Significantly lower DNA repair efficiency of the X-rays induced damage was observed in PAHs-exposed donors (66.0% vs 76.4%, p<0.003 in the winter sampling; 57.7% vs 69.0%, p<0.004 in the summer sampling). Reduced repair efficiencies were observed in cells of donors exposed to PAHs after stratification according to smoking history (i.e. 54.2% vs 64.9%, p<0.05 in the smokers subgroup in summer sampling). Stratification according to genotype of donors was also done. Donors exposed to PAHs and heterozygous with the mutation in CYP1A1 gene (Ile/Val), despite much smaller number of such donors, exhibited significantly lower efficiency of repair (34.3% vs 62.7%, p<0.04). Donors belonging to the subgroup of slow acetylators (according to NAT2 genotype) who were exposed to PAHs were significantly less efficient in repair (64.7% vs 78.0%, p<0.006 in the winter sampling). Significantly reduced repair efficiencies were also observed for donors exposed to PAHs with deletion in GSTM1 gene (55.3% vs 66.9%, p<0.003 in the summer sampling). Our results illustrate, that application of X-rays dose to study DNA repair competence can be a good predictive biomarker in human monitoring studies. Obtained results imply that environmental exposure to polycyclic aromatic hydrocarbons via alteration of cellular DNA repair processes can result in effects harmful to human health. From our studies can be concluded that lowering of DNA repair efficacy increases amount of unrepaired DNA damage in lymphocytes of exposed to PAHs donors, that may elevate frequency of mutations and increase their risk of cancer

Chromosomal aberrations and SCEs as biomarkers of cancer risk

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

Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results:: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P = .038) and 11% lower concentration of UA (P = .005). TOS was 20% lower (P = .014). The activity of SOD was up to 5% higher (P = .037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes