Agricultural exposures and DNA damage in PBMC of female farmers measured using the alkaline comet assay.

OBJECTIVE: Several studies investigated the link between agricultural occupational exposures and DNA damage, in an attempt to bring elements of biological plausibility to the increased cancer risk associated with them. However, only a few of these studies focused on females. METHODS: The comet assay was performed on PBMC (Peripheral Blood Mononuclear Cells) samples from 245 females working in open field farming and cattle raising, located in the Normandy area of France. Individual questionnaires on tasks performed were administered at the time of sampling to directly assess exposures. Environmental exposures were issued from a questionnaire assessing the farm productions. Linear regression analyses were done using the DNA damage scores. RESULTS: Regarding direct exposures, several tasks associated with exposure to potentially harmful chemicals were not associated with DNA damage, but a longer duration of use of herbicide on meadows (p = 0.05) or of cleaning and upkeep of agricultural equipment (p = 0.06) revealed higher DNA damage levels, although the number of exposed women was low. Several indirect and/or environmental exposures were associated with DNA damage in multivariate analyses: a larger surface of meadows (p = 0.006) or the presence of poultry (p = 0.03) was associated with less DNA damage, while the presence of swine (p = 0.01) was associated with higher DNA damage. Smokers and former smokers had less DNA damage than non-smokers (p = 0.0008 and p = 0.03). CONCLUSIONS: We report modified levels of DNA damage for those environmentally exposed to meadows, poultry and pig farming, underlining the need for a better knowledge of the potential health risks experienced by females in this setting.

Early-morning OFF and levodopa dose failures in patients with Parkinson's disease attending a routine clinical appointment using Time-to-ON Questionnaire.

BACKGROUND AND PURPOSE: In patients with Parkinson's disease (PD) with motor fluctuations, total daily OFF time is comprised of both end-of-dose time and the time taken to turn ON with medication. However, little is known about the impact of delays in ON time. METHODS: This was a single-visit pilot study of fluctuating patients with PD attending a routine appointment. During a single visit, adult patients with idiopathic PD who were treated with levodopa for at least 1 year completed a questionnaire evaluating the time waiting for ON and the symptoms experienced while waiting to turn ON. Patients then completed a 5-day home time-to-ON diary, where they documented how long it took to turn ON following their first morning dose of levodopa in 5-min increments. RESULTS: A total of 151 consecutive patients completed the study survey, of whom 97 (64.2%) experienced motor fluctuations. Of the patients experiencing motor fluctuations, 54 (56%) reported delays in ON time (latency >30 min) following their first morning dose of levodopa. Half (51%) reported that they had experienced delayed ON at least once in the previous week and 21% reported having delayed ON during all seven mornings of the previous week. In addition, 10% of patients reported having dose failures on four or more mornings during the previous week. The most common symptoms experienced while waiting for ON were slowness (94.8%), fatigue (87.6%), reduced dexterity (82.5%), problems in walking (66.0%) and problems with balance (59.8%). CONCLUSION: Early-morning OFF problems such as delays in time to ON and dose failures are common in levodopa-treated patients with PD.

The phenotype of migraine with unilateral cranial autonomic symptoms documents increased peripheral and central trigeminal sensitization. A case series of 757 patients.

BACKGROUND: Migraine with unilateral cranial autonomic symptoms (UAS) is a putative migraine endophenotype with convincing response to trigeminal-targeted treatments that still needs a thorough characterization. OBJECTIVE: The objective of this article is to carefully investigate the clinical phenotype of migraine with UAS in a large group of patients for more accurate migraine diagnoses, improved clinical management, and better outcome prediction. METHODS: We studied 757 consecutive episodic and chronic migraineurs in a tertiary headache clinic with face-to-face interviews, detailing in depth their lifestyle, sociodemographic and headache characteristics. RESULTS: Migraineurs with UAS (37.4%) differed from the general migraine population with respect to longer attack duration (OR = 2.47, p < 0.02, having >72-hour long attacks), more strictly unilateral (OR = 3.18, p < 0.001) and severe headache (OR = 1.72, p = 0.011), more frequent allodynia (OR = 3.03, p < 0.001) and photophobia (OR = 1.87, p = 0.019). CONCLUSIONS: Migraine patients with UAS are characterized not only by symptoms due to intense peripheral trigeminal activation but also to central sensitization. Our study broadens the knowledge on the clinical and phenotypic characteristics of migraine with UAS, suggests pathophysiological implications, and supports the need for future prospective clinical studies.

Biomonitoring of several toxic metal(loid)s in different biological matrices from environmentally and occupationally exposed populations from Panasqueira mine area, Portugal.

In the Panasqueira mine area of central Portugal, some environmental media show higher metal(loid) concentrations when compared with the local geochemical background and the values proposed in the literature for these environmental media. In order to evaluate the effect of the external contamination on selected indexes of internal dose, As, Cd, Cu, Cr, Fe, Hg, Mg, Mn, Mo, Ni, Pb, S, Se, Si, and Zn were quantified by inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry in blood, urine, hair and nail samples from individuals environmentally (N = 41) and occupationally exposed (N = 41). A matched control group (N = 40) was also studied, and data from the three groups were compared. Results obtained agreed with those reported by environmental studies performed in this area, pointing to populations living nearby and working in the mine being exposed to metal(loid)s originated from mining activities. Arsenic was the element with the highest increase in exposed populations. The concentration of other elements such as Cr, Mg, Mn, Mo, Ni, Pb, S, Se, and Zn was also increased, although at a lesser extent, specifically in the individuals environmentally exposed and in females. These findings confirm the need for competent authorities to act as soon as possible in this area and implement strategies aimed to protect exposed populations and the entire ecosystem.

E-learning to improve the drug prescribing in the hospitalized elderly patients: the ELICADHE feasibility pilot study.

BACKGROUND: E-learning is an efficient and cost-effective educational method. AIMS: This study aimed at evaluating the feasibility of an educational e-learning intervention, focused on teaching geriatric pharmacology and notions of comprehensive geriatric assessment, to improve drug prescribing to hospitalized elderly patients. METHODS: Eight geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control. Clinicians of the two groups had to complete a specific per group e-learning program in 30 days. Then, ten patients (aged ≥75 years) had to be consecutively enrolled collecting clinical data at hospital admission, discharge, and 3 months later. The quality of prescription was evaluated comparing the prevalence of potentially inappropriate medications through Beer's criteria and of potential drug-drug interactions through a specific computerized database. RESULTS: The study feasibility was confirmed by the high percentage (90 %) of clinicians who completed the e-learning program, the recruitment, and follow-up of all planned patients. The intervention was well accepted by all participating clinicians who judged positively (a mean score of >3 points on a scale of 5 points: 0 = useless; 5 = most useful) the specific contents, the methodology applied, the clinical relevance and utility of e-learning contents and tools for the evaluation of the appropriateness of drug prescribing. CONCLUSIONS: The pilot study met all the requested goals. The main study is currently ongoing and is planned to finish on July 2015.

Prognostic factors and outcomes in Italian patients undergoing curative gastric cancer surgery.

BACKGROUND: Survival of patients after curative surgical resection for gastric cancer (GC) remains poor, thus emphasizing the need for better definition of prognostic factors to improve the long-term course of disease. METHODS: From 1999 to 2009, 110 patients had curative-intent gastrectomy for adenocarcinoma. Clinicopathological features, Helicobacter pylori infection, dietary habits and lifestyle, and the presence of proinflammatory gene polymorphisms were evaluated. RESULTS: At the end of follow-up, 55 deaths had occurred, 48 of them due to GC, whereas the median overall survival (OS) and disease-free survival (DFS) were 62 and 51 months, respectively. From the Kaplan-Meier analysis and log-rank test, statistically significant differences in OS and DFS were found for tumor site (only for DFS), tumor size, lymph node metastasis ratio (NR), and tumor-node-metastasis stage, but not for age, comorbidity, H. pylori infection, cigarette smoking, and IL1B or TNFA polymorphisms. Multivariable Cox regression analysis revealed NR was an independent prognostic factor for OS and DFS. Cardia tumor and patient age 65 years or older were also independent prognostic factors for OS and DFS. CONCLUSIONS: Tumor-related factors remain strongest predictors of survival in GC patients after surgery. Particularly, NR was an effective feature in identifying patients at high risk for adverse outcome.

Small-bore wire-guided chest drains: safety, tolerability, and effectiveness in pneumothorax, malignant effusions, and pleural empyema.

BACKGROUND: The use of small-bore wire-guided chest drains for pleural effusions and pneumothorax has become popular; however, limited data are available on its efficacy and morbidity. The aim of this retrospective study is to measure, via the analysis of the so far largest reported cohort, the efficacy, safety, and tolerability of this approach in different clinical conditions. METHODS: In the period from January 2002 to December 2008, 1092 patients have undergone the positioning of a small-bore wire-guided chest drain (12F) for the evidence of pneumothorax or pleural effusion and have been monitored over time for morbidity, pain at the time of insertion (measured via the visual analogue scale), and drain failure for misplacement or blockage. Patients with trauma were excluded from this study. RESULTS: Male/female ratio and mean age were respectively 418:674 and 55.85 ± 18.6. Three-hundred ninety-nine (36.5%) drains were inserted for pneumothorax, 324 (29.7%) for malignant effusion, 97 (8.9%) for empyema, and 272 (24.9%) for nonmalignant effusion. The pain experience was on average "very mild" (mean visual analogue scale = 4.6 mm). The overall drain failure rate was 12.9%. The percentage of successful cases was 93.8% in malignant effusion, 93% in pneumothorax, and 92.3% in nonmalignant effusion; in the cases of pathologically diagnosed empyema, drains were more likely to get blocked (74.2%). We recorded 1 serious complication within the malignant effusion group. CONCLUSIONS: Wire-guided 12F Seldinger-type drains are a well-tolerated and effective method of treating pneumothorax and uncomplicated pleural effusions (malignant and nonmalignant) with acceptable morbidity. The use of 12F small-bore chest drain is not indicated for the treatment of empyema.

Transcriptomic network analysis of micronuclei-related genes: a case study.

Mechanistically relevant information on responses of humans to xenobiotic exposure in relation to chemically induced biological effects, such as micronuclei (MN) formation can be obtained through large-scale transcriptomics studies. Network analysis may enhance the analysis and visualisation of such data. Therefore, this study aimed to develop a 'MN formation' network based on a priori knowledge, by using the pathway tool MetaCore. The gene network contained 27 genes and three gene complexes that are related to processes involved in MN formation, e.g. spindle assembly checkpoint, cell cycle checkpoint and aneuploidy. The MN-related gene network was tested against a transcriptomics case study associated with MN measurements. In this case study, transcriptomic data from children and adults differentially exposed to ambient air pollution in the Czech Republic were analysed and visualised on the network. Six genes from the network, i.e. BAX, DMNT1, PCNA, HIC1, p21 and CDC20, were retrieved. Based on these six genes and in combination with p53 and IL-6, a dedicated network was created. This dedicated network is possibly suited for the development of a reporter gene assay that could be used to screen populations complementary to the current MN test assay. In conclusion, we have shown that network analysis of transcriptomics data in relation to the formation of MN is possible and provides a novel mechanistic hypothesis by indicating which genes are regulated and influence others.

SV40 associated miRNAs are not detectable in mesotheliomas.

BACKGROUND: Simian virus-40 (SV40) is a DNA tumour virus that was introduced into the human population with contaminated poliovirus vaccine, and its role in mesothelioma is widely debated. PCR based testing has been called into question, as false positives can be because of cross-reactivity with related viruses, or to laboratory contamination. The Institute of Medicine has recommended the development of more sensitive and specific tests to resolve this controversy. METHODS: We have characterized highly sensitive RT-PCR based assays that are specific for SV40-encoded microRNAs (miRNAs), as an alternative to current testing methods. RESULTS: Using this sensitive and specific detection method, we were unable to identify SV40 miRNA expression in human malignant pleural mesothelioma (MM) samples. CONCLUSION: Our work indicates that SV40 miRNAs are not likely to contribute to mesothelioma tumourogenesis, but highlights the value of this approach when compared with the relatively unspecific current testing methods.

Spectral analysis of the voice in Down Syndrome.

The voice quality of individuals with Down Syndrome (DS) is generally described as husky, monotonous and raucous. On the other hand, the voice of DS children is characterized by breathiness, roughness, and nasality and is typically low pitched. However, research on phonation and intonation in these participants is limited. The present study was designed to provide data from the spectral analysis of the human voice in DS people. A cross-sectional, observational design was applied. Thirty DS adults and 48 DS children were enrolled after clinical evaluation. Thirty men, 30 women and 46 children constituted the control group. The participants had to repeat a set of Italian words twice. The Real Time Pitch software manufactured by KayPENTAX recorded the voice. The following spectral descriptors were obtained for each word: Mean Frequency and standard deviation, Energy, Duration, Jitter and Shimmer. Test-retest performance was also checked. The voice of DS adults was characterized by a significantly higher Mean Frequency, particularly in males (p<0.0001), by a smaller variation (p=0.0044 in males and p=0.0046 in females) and by a significantly lower level of Energy (p=0.0037 in males and p=0.0025 females). Furthermore, limited to male adults, a shorter Duration (p=0.0156) and a smaller value of Shimmer (p=0.0014) was observed. The difference between DS children and age-matched controls was limited, reaching significance only for the Coefficient of Variation (CV) (p=0.031). The difference in Mean Frequency between adults and children was more evident in the control males than in all other groups. The lack of marked difference between voice characteristics of children with and without DS is outlined by findings. Pearson's correlation coefficients on repeated productions ranged from 0.23 (Jitter) to 0.86 (Mean Frequency) in children, and from 0.07 (Shimmer) to 0.86 (Mean Frequency) in adults. In the control group, all the coefficients ranged between 0.85 and 0.98. As expected, women had a higher Mean Frequency than men, but the CV was around 0.1 for both. By contrast, children had a significantly higher Mean Frequency and a lower CV. In conclusion, spectral analysis of the human voice is recommended in each laboratory of speech and language rehabilitation to exploit the accuracy of voice descriptors.

Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery.

OBJECTIVE: We have analyzed short- and long-term variations of pulmonary function in locally advanced non-small cell lung cancer after induction chemoradiotherapy. METHODS: Twenty-seven patients with stage IIIA (N2) non-small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. RESULTS: A 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, -20.50% (P < .001); forced vital capacity, -22.50% (P < .001); forced expiratory volume in 1 second, -23.00% (P < .001); peak expiratory flow, -29.0 (P < .001); forced expiratory flow 25% to 75%, -13.7% (P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% (P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase (P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. CONCLUSIONS: An impairment of respiratory function is evident in the immediate postoperative setting in patients with non-small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only.

Gender-related differences in response to mutagens and carcinogens.

The incidences of many cancers can be very different in men and women. Besides differences in exposures to putative causative agents, it is plausible that both genetic and epigenetic effects play roles in these differences. In addition, gender-specific lifestyle and behavioural factors may modulate the effects of exposure to genotoxins. This commentary focuses on several aspects of gender-related differences in responses to mutagens and carcinogens, including sensitivity to chromosome damage, the contribution of genotypic variation and the role of DNA methylation. It is concluded that the reasons for gender differences in cancer susceptibility remain largely unknown in many cases, and the subject deserves more attention and study.

Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis.

Micronuclei (MN) frequency is a biomarker of chromosomal damage, genome instability, and cancer risk that integrates acquired mutations and genetic susceptibility. To evaluate and summarize the evidence reporting association between cancer and MN formation, we performed a meta-analysis assessing the frequency of this biomarker in cancer patients. Findings from 37 publications were retrieved through an extensive search of the MedLine/PubMed database. Given the heterogeneity of the study design, all studies were re-classified into three groups: (i) baseline MN frequency of untreated cancer patients (25 studies), (ii) induced MN frequency in thyroid cancer patients undergoing radioiodine treatment (9 studies), and (iii) radiosensitivity of lymphocytes (12 studies) in untreated cancer patients. A meta-estimate of the frequency ratio (meta-FR) was computed in each group. A significant increase of MN frequency was found in untreated cancer patients (meta-FR=1.45; 95% Confidence Interval (95% CI): 1.28-1.64) and in thyroid cancer patients after radioiodine treatment (meta-FR=2.26; 95% CI: 1.90-2.68). The third meta-analysis showed a negative trend of meta-FR's when plotted vs. the dose used to study patients' radiosensitivity, possibly associated to a high rate of apoptosis. The results of this review substantiate the existing evidence about a role of MN in various steps of carcinogenesis. The relatively small numbers of papers suitable for the meta-analysis call for new and larger studies, possibly based on high-throughput techniques, to further understand the role of MN formation in the occurrence of genetic instability and cancer.

Prevalence of post-partum thyroiditis in Liguria (Italy): an observational study.

BACKGROUND: Post-partum thyroiditis (PPT) is an autoimmune disorder occurring within the first year following delivery. A variable prevalence has been reported in different surveys. We prospectively evaluated PPT prevalence and outcome in a cohort of pregnant women living in a well-defined geographic area. AIM: A subset from a group of healthy women consecutively evaluated for thyroid function and thyroid autoimmunity during pregnancy, referring to the same obstetric unit, were followed up at 4-6 months and 1 yr after delivery. MATERIALS/SUBJECTS AND METHODS: Follow-up for PPT was performed in 258 pregnant women. Control data were obtained in a comparable group of healthy non-pregnant women. Free T3 (fT3), free T4 (fT4), TSH thyroglobulin/thyroid peroxidase autoantibodies (TgAb/TPOAb), and urinary iodine excretion were measured. RESULTS: Autoantibody positivity was observed in 9.3% of pregnant, similar to control women. Forty-three out of 59 autoantibody-positive women were followed up; 23 showed PPT at the first control, 18 had hypothyroidism at 1 yr (5 had not shown PPT at the first control). Among 215 out of 584 autoantibody-negative women followed up, 27 developed PPT (15 of them without thyroid autoantibodies); 16 developed thyroid autoantibodies without PPT. After 1 yr, 9 women had hypothyroidism: only 1 of them was autoantibody-negative at the former control. Urinary iodine was increased in several pregnant women. CONCLUSIONS: An overall PPT prevalence of about 18% may be estimated. PPT was also observed in autoantibody- negative women. Differences with other surveys may be related to both study protocol and characteristics of the population studied.

Genetic polymorphisms and micronucleus formation: a review of the literature.

The formation of micronuclei (MN) is extensively used in molecular epidemiology as a biomarker of chromosomal damage, genome instability, and eventually of cancer risk. The occurrence of MN represents an integrated response to chromosome-instability phenotypes and altered cellular viabilities caused by genetic defects and/or exogenous exposures to genotoxic agents. The present article reviews human population studies addressing the relationship between genetic polymorphisms and MN formation, and provides insight into how genetic variants could modulate the effect of environmental exposures to genotoxic agents, host factors (gender, age), lifestyle characteristics (smoking, alcohol, folate), and diseases (coronary artery disease, cancer). Seventy-two studies measuring MN frequency either in peripheral blood lymphocytes or exfoliated cells were retrieved after an extensive search of the MedLine/PubMed database. The effect of genetic polymorphisms on MN formation is complex, influenced to a different extent by several polymorphisms of proteins or enzymes involved in xenobiotic metabolism, DNA repair proteins, and folate-metabolism enzymes. This heterogeneity reflects the presence of multiple external and internal exposures, and the large number of chromosomal alterations eventually resulting in MN formation. Polymorphisms of EPHX, GSTT1, and GSTM1 are of special importance in modulating the frequency of chromosomal damage in individuals exposed to genotoxic agents and in unexposed populations. Variants of ALDH2 genes are consistently associated with MN formation induced by alcohol drinking. Carriers of BRCA1 and BRCA2 mutations (with or without breast cancer) show enhanced sensitivity to clastogens. Some evidence further suggests that DNA repair (XRCC1 and XRCC3) and folate-metabolism genes (MTHFR) also influence MN formation. As some of the findings are based on relatively small numbers of subjects, larger scale studies are required that include scoring of additional endpoints (e.g., MN in combination with fluorescent in situ hybridization, analysis of nucleoplasmic bridges and nuclear buds), and address gene-gene interactions.

Exposure to genotoxic agents, host factors, and lifestyle influence the number of centromeric signals in micronuclei: a pooled re-analysis.

We pooled data from three biomonitoring studies using the cytokinesis-block micronucleus assay in peripheral blood lymphocytes in combination with fluorescence in situ hybridization. Centromere-positive micronuclei (C+MN) were classified in two groups: those containing one centromere (C1+MN) and those with two or more (Cx+MN). The three studies evaluated untreated cancer patients, welders, and pathologists/anatomists exposed to formaldehyde. The total number of subjects included in the pooled re-analysis was 113. A higher frequency of C+MN was observed in cancer patients and exposed workers, who showed significant differences from controls in all studies. C1+MN were particularly increased in the group of pathologists/anatomists, who showed a 3.29 times higher frequency than controls (95% CI: 2.04-5.30). A borderline increase in Cx+MN was observed in welders when compared to the corresponding control group (FR: 1.31; 95% CI: 0.99-1.74). An evident effect of gender was found, with significantly increased frequencies of all endpoints measuring aneuploidy in females (C+MN, C1+MN, and Cx+MN). Alcohol consumption had a significant effect on total MN frequency and particularly on C+MN and C1+MN. In conclusion, scoring the number of centromeric signals in the micronucleus assay provides additional information about the mechanism of action of various genotoxic agents, and the role of confounding factors may be more specifically accounted for. Indeed, C+MN could be efficiently used in biomonitoring studies as an independent biomarker of exposure and early biological effect. The use of centromeric signals allows the identification of two further endpoints, representing two alternative pathways of chromosome loss, i.e., impaired chromosome migration, leading to increased C1+MN frequency, and centrosome amplification, possibly leading to Cx+MN with two or more centromeric signals.

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer.

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.

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.