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Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls. In colorectal cancer (CRC) patients, only CTAs were significantly elevated. Binary logistic regression, adjusted for main confounders, indicates that all the analysed cytogenetic parameters along with smoking were significantly associated with breast and lung cancer risks. Significant differences in terminal deletions between breast cancer patients and corresponding female controls were recorded (0.39 vs. 0.18; P ≤ 0.05). We did not find any association of CAs with TNM (tumor nodus metastasis) stages or histopathological grade in either cancer type. CAs were neither associated with additional tumor characteristics-invasivity, ductal and lobular character, estrogene/progesterone receptors in breast tumors nor with non-small/small cell and bronchogenic/pulmonary types of lung tumors. Our study demonstrates that CAs serve as a predictive marker for breast and lung cancer, whereas only CTAs were elevated in incident CRC patients., (© The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Structural chromosomal aberrations in blood lymphocytes represent a biomarker for cellular damage caused by genotoxic carcinogens and are an indicator of increased cancer risk. We evaluated the association between frequencies of total chromosomal aberrations, chromatid- and chromosome-type aberrations, and occupational exposures to volatile anesthetics, antineoplastic agents, and formaldehyde among 601 medical professionals., Methods: Chromosomal damage among exposed individuals and unexposed controls was determined by conventional cytogenetic analysis. We used binary logistic regression to evaluate the effects of workplace exposures and major confounders on chromosomal damage., Results: Significantly higher frequencies of total chromosomal, chromatid-type and chromosome-type aberrations were observed among subjects occupationally exposed to volatile anesthetics, antineoplastic agents, and formaldehyde compared to age- and sex-matched controls (P<0.0001). The risk of an increased frequency of chromosomal aberrations was associated with exposure to anesthetics [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 2.7-5.8], cytostatics (OR 2.7, 95% CI 1.9-3.9), and formaldehyde (OR 1.7, 95% CI 1.1-2.7). No other covariate contributed significantly to the model. Chromatid- and chromosome-type aberrations were associated with exposure to anesthetics and cytostatics without any contribution of other variables. Stratified data analysis showed the risk of increased chromosomal aberrations among non-smoking female nurses and physicians exposed to anesthetics, cytostatics and, partially, formaldehyde. Chromatid and chromosome exchanges were significantly higher in the exposed groups than among controls., Conclusion: Our findings indicate that the presence of genotoxic compounds in operating rooms, oncological units, and pathological departments results in a significant increase of chromosomal damage (impair of chromosomal integrity) among medical workers employed in these facilities.

Purpose: Welders have been chronically exposed to hexavalent chromium with potential consequences on chromosomal integrity. Our study is focused on the extent of any such chromosomal aberrations with respect to chromium levels in the blood of welders as well as on the tentative modulating role of polymorphisms in DNA repair genes XPD Lys751Gln, XPG Asn114His, XPC Lys939Gln, hOGG1 Ser326Cys and XRCC1 Arg399Gln on chromosomal damage., Methods: The study was conducted on 144 individuals consisting of 73 welders exposed to chromium for 10.2 ± 1.67 years and 71 control individuals without known exposures. Chromosomal aberrations, their chromatid-type and chromosome-type aberrations were detected by conventional cytogenetic analysis. XPD, XPG, XPC, hOGG1 and XRCC1 gene polymorphisms were assayed for by Taqman SNP genotyping assay ("Assay-by-Demand") using Real-Time allelic discrimination on AB 7500 equipment. Chromium concentration in the blood was determined by atomic absorption spectrophotometry., Results: The level of chromium in the blood of welders ranged between 0.032 and 0.182 μmol l(-1) and was significantly higher than that in controls (0.07 ± 0.04 μmol l(-1) vs. 0.03 ± 0.007 μmol l(-1)). Parameters of chromosomal damage were similar in both the exposed and the control individuals (1.89% vs. 1.70% for total chromosomal aberrations, 0.97% vs. 0.88% for chromosome-type and 0.92% vs. 0.80% for chromatid-type, respectively). Chromatid-type of aberrations positively correlated with the level of chromium in the blood (r = 0.28; P = 0.02). Significantly higher total chromosomal aberrations were detected in individuals with homozygous variant polymorphism in XRCC1 Arg399Gln gene as compared to those with heterozygous and homozygous wild-type genotypes (2.20, 1.89 and 1.48%, respectively; P = 0.01). A similar tendency was found for chromatid-type aberrations (1.30% for homozygous variant genotype bearers, 0.94% for those with heterozygous genotype and 0.75% for carriers of homozygous wild-type genotype, respectively; P = 0.04)., Conclusions: Although no apparent increase in chromosomal damage was recorded in chromium-exposed welders in comparison with controls, genetic make-up in DNA repair genes may increase susceptibility toward adverse effect of chromium.

We evaluated chromosomal aberrations in lymphocytes of 177 workers exposed to xenobiotics in a tire plant and in 172 controls, in relation to their genetic background. Nine polymorphisms in genes encoding biotransformation enzymes and nine polymorphisms in genes involved in main DNA repair pathways were investigated for possible modulation of chromosomal damage. Chromosomal aberration frequencies were the highest among exposed smokers and the lowest in non-smoking unexposed individuals (2.5+/-1.8% vs. 1.7+/-1.2%, respectively). The differences between groups (ANOVA) were borderline significant (F=2.6, P=0.055). Chromosomal aberrations were higher in subjects with GSTT1-null (2.4+/-1.7%) than in those with GSTT1-plus genotype (1.8+/-1.4%; F=7.2, P=0.008). Considering individual groups, this association was significant in smoking exposed workers (F=4.4, P=0.040). Individuals with low activity EPHX1 genotype exhibited significantly higher chromosomal aberrations (2.3+/-1.6%) in comparison with those bearing medium (1.7+/-1.2%) and high activity genotype (1.5+/-1.2%; F=4.7, P=0.010). Both chromatid- and chromosome-type aberration frequencies were mainly affected by exposure and smoking status. Binary logistic regression analysis revealed that frequencies of chromatid-type aberrations were modulated by NBS1 Glu185Gln (OR 4.26, 95%CI 1.38-13.14, P=0.012), and to a moderate extent, by XPD Lys751Gln (OR 0.16, 95%CI 0.02-1.25, P=0.081) polymorphisms. Chromosome-type aberrations were lowest in individuals bearing the EPHX1 genotype conferring the high activity (OR 0.38, 95%CI 0.15-0.98, P=0.045). Present results show that exposed individuals in the tire production, who smoke, exhibit higher chromosomal aberrations frequencies, and the extent of chromosomal damage may additionally be modified by relevant polymorphisms.