Serum Calretinin as a Biomarker in Malignant Mesothelioma.

The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.

The role of polymorphisms in glutathione-related genes in asbestos-related diseases.

BACKGROUND: The study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM). SUBJECTS AND METHODS: The cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used. RESULTS: GSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40-0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28-0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00-1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03-0.85; p = 0.031). CONCLUSIONS: Our findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.

NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases.

BACKGROUND: This study aimed to investigate the association between NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms and the risk of developing pleural plaques, asbestosis, and malignant mesothelioma (MM), and to study the influence of the interactions between polymorphisms and asbestos exposure on the risk of developing these diseases. METHODS: The case-control study included 416 subjects with pleural plaques, 160 patients with asbestosis, 154 subjects with MM and 149 subjects with no asbestos disease. The NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms were determined using real-time PCR-based methods. In the statistical analysis, standard descriptive statistics was followed by univariate and multivariate logistic regression modelling. RESULTS: Asbestos exposure (medium and high vs low) was associated with the risk for each studied asbestos-related disease. An increased risk of pleural plaques was found for CARD8 rs2043211 at + TT genotypes (OR = 1.48, 95% CI 1.01-2.16, p = 0.042). When the analysis was performed for MM patients as cases, and pleural plaques patients as controls, a decreased MM risk was observed for carriers of CARD8 rs2043211 TT genotype (OR = 0.52, 95% CI 0.27-1.00, p = 0.049). The interactions between NLRP3 rs35829419 and CARD8 rs2043211 genotypes did not influence the risk of any asbestos-related disease. However, when testing interactions with asbestos exposure, a decreased risk of asbestosis was found for NLRP3 CA+AA genotypes (OR = 0.09, 95% CI 0.01-0.60, p = 0.014). CONCLUSIONS: The results of our study suggest that NLRP3 and CARD8 polymorphisms could affect the risk of asbestos-related diseases.

Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases.

Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.

The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma.

BACKGROUND: Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual's susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk. PATIENTS AND METHODS: In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms. RESULTS: The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83-17.98] and slightly with age, OR 1.10 (95% CI: 1.08-1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59-13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02-2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95% CI 0.10-0.77). CONCLUSIONS: Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.

Restructuring of a Textile Manufacturing Company and Workers' Health.

Organizational restructuring is associated with greater mortality and morbidity of the workers affected by it. We examined the quality of workers' health at a textile manufacturing company after restructuring, comparing three groups of workers: workers who remained (survivors), workers who lost their jobs and later found new jobs (the reemployed), and unemployed workers. A total of 1046 workers participated in a telephonic survey. The data were processed using SPSS and the R package version 1.2 of prLogistic. The differences between groups were calculated using the chi-square test and adjusted prevalence ratios. The comparison between the three groups shows significantly poorer mental health of the unemployed, who more often than survivors and the reemployed reported depression, as well as significant differences in elevated blood pressure, cholesterol level, and cardiac disorders. The reemployed, who were nonetheless in better health compared to the unemployed, reported poor mental health or depression more often in comparison to survivors. Higher morbidity of the unemployed and reemployed could be influenced by numerous factors associated with restructuring.

Patients' Risk of Causing Traffic Violations and Traffic Accidents while Driving.

OBJECTIVES: This study examines whether drivers suffering from epilepsy, chronic alcoholism and/or hazardous drinking, psychoactive substance abuse, other diseases of the nervous system, mental and behavioural disorders, cardiovascular diseases, severe diabetes, and severe eye diseases are at a greater risk of causing traffic accidents and traffic violations than drivers that cause accidents and violations without these diagnoses. METHODS: A case control study was carried out. The cases were drivers checked by a special medical committee in the period observed suffering from the diseases listed above. Matched controls were taken from the cohort of those that caused accidents and violations during the same period observed. The descriptive statistics were followed by calculation of correlations, t-tests and χ2, and the odds ratio. RESULTS: Drivers with referrals for diseases of the nervous system are five times more likely to cause a traffic accident compared to controls (OR=5.18; 95% CI=2.59-10.34); in addition, a high risk is associated with drivers with mental and behavioural disorders (OR=3.64; 95% CI=1.91-6.94), drivers with epilepsy (OR=1.99; 95% CI=1.01-3.92), and drivers addicted to alcohol (OR=1.71; 95% CI=1.01-2.89). CONCLUSION: Drivers suffering from addiction, a disease of the nervous system, or epilepsy are more likely to cause a traffic accident, which is a contribution to the inconclusive findings of previous studies. The multiple reasons for risks of patients suffering from mental and behavioural disorders need to be further investigated.

Serum Survivin Levels and Outcome of Chemotherapy in Patients with Malignant Mesothelioma.

BACKGROUND: Survivin is an inhibitor of apoptosis protein involved in the regulation of cell proliferation that could be used as a marker for cancer diagnosis or prognosis. Our aim was to evaluate whether serum survivin levels influence the outcome of cisplatin-based chemotherapy in patients with malignant mesothelioma (MM). METHODS: Serum survivin levels were determined using human survivin enzyme-linked immunosorbent assay in 78 MM patients before chemotherapy, after chemotherapy, and at disease progression. The influence on tumor response and survival was evaluated using nonparametric tests and Cox regression. RESULTS: A median serum survivin level at diagnosis was 4.1 (0-217.5) pg/mL. Patients with a progressive disease had significantly higher survivin levels before chemotherapy (p = 0.041). A median serum survivin level after chemotherapy was 73.1 (0-346.2) pg/mL. If survivin levels increased after chemotherapy, patients had, conversely, better response (p = 0.001, OR = 5.40, 95% CI = 1.98-14.72). Unexpectedly, patients with increased survivin levels after chemotherapy also had longer progression-free (p < 0.001, HR = 0.33, 95% CI = 0.20-0.57) and overall survival (p = 0.001, HR = 0.29, 95% CI = 0.14-0.58). CONCLUSIONS: These results suggest that serum survivin levels before and during chemotherapy could serve as a biomarker predicting MM treatment response.

Fibulin-3 as a biomarker of response to treatment in malignant mesothelioma.

BACKGROUND: Fibulin-3 is a new potential biomarker for malignant mesothelioma (MM). This study evaluated the potential applicability of fibulin-3 plasma levels as a biomarker of response to treatment and its prognostic value for progressive disease within 18 months. The potential applicability of fibulin-3 in comparison with or in addition to soluble mesothelin-related peptides (SMRP) was also assessed. PATIENTS AND METHODS: The study included 78 MM patients treated at the Institute of Oncology Ljubljana between 2007 and 2011. Fibulin-3 levels in plasma samples obtained before treatment and in various responses to treatment were measured with the enzyme-linked immunosorbent assay. RESULTS: In patients evaluated before the treatment, fibulin-3 levels were not influenced by histopathological sub-types, tumour stages or the presence of metastatic disease. Significantly higher fibulin-3 levels were found in progressive disease as compared to the levels before treatment (Mann-Whitney [U] test = 472.50, p = 0.003), in complete response to treatment (U = 42.00, p = 0.010), and in stable disease (U = 542.00, p = 0.001). Patients with fibulin-3 levels exceeding 34.25 ng/ml before treatment had more than four times higher probability for developing progressive disease within 18 months (odds ratio [OR] = 4.35, 95% confidence interval [CI] 1.56-12.13). Additionally, patients with fibulin-3 levels above 34.25 ng/ml after treatment with complete response or stable disease had increased odds for progressive disease within 18 months (OR = 6.94, 95% CI 0.99-48.55 and OR = 4.39, 95% CI 1.63-11.81, respectively). CONCLUSIONS: Our findings suggest that in addition to SMRP fibulin-3 could also be helpful in detecting the progression of MM.

The Influence of Workers' Health Status on Employers' Decision-Making During Personnel Restructuring in a Typical Public Limited Enterprise in Slovenia.

OBJECTIVES: Alongside individual indicators of job performance, even workers' health status could be a criterion for selection. The mechanisms for health selection are a reduction of productivity in relation to illness or certain health behaviour. The aim of the study was to establish how indicators of workers' health status, which are accessible to the employer, influence the employer's decision-making on which workers to retain and which to dismiss during personnel restructuring in the enterprise. METHODS: Due to a planned closure of a plant, the observed company began personnel restructuring which included a strategic decrease in the number of employees and the relocation of workers within the company. Two nested case control studies were conducted. The cases were divided into two groups and defined as follows: employees who were relocated and employees whose employment contract was terminated. RESULTS: The results show that the disability category and long-time sick leave exert the greatest influence on the employer's decision on the selection of workers. Workers with work-related disability have lower odds to be relocated to a new workplace (OR=0.5; 95% CI 0.2 to 1.1) and higher odds to be dismissed (OR=6.51; 95% CI 3.33 to 12.72). The workers with a history of a long-time sick leave also have lower odds to be relocated (OR=0.31; 95% CI 0.11 to 0.88) and higher odds to be dismissed (OR=4.32; 95% CI 2.08 to 8.96). CONCLUSIONS: Indicators of health which were accessible to the employer actually exerted influence on the employer's decision-making, which could show a direct form of health selection.

Sickness Presence among Disabled Workers at the University Medical Centre Ljubljana.

OBJECTIVES: The aim of the article is to investigate the differences in sickness present and non-sickness present in the group of disabled health care professionals. METHODS: Data were gathered from all disabled health care professionals suffering from invalidity of category II or III who were identified in the research among all health care professionals at the University Medical Centre Ljubljana and who were employed there in the period between 1 January 2010 and 31 December 2010. Each employee obtained a questionnaire composed of three standardized international questionnaires. RESULTS: There were 248 disabled workers of the II. and III. category of invalidity among the participants. Disabled sickness present reported to have more chronic diseases than disabled non-sickness present (OR = 57.0; 95% CI = 24.4-133.2), lower salary when on sick leave (OR = 13.1; 95% CI = 5.7-30.2) and poor self-rated health (OR = 5.8; 95% CI = 2.7-12.3). CONCLUSIONS: The prerequisite for sickness presence among disabled workers is their chronic bad health. It is also formally recognized with the degree of disability. Economic factors are among the most important to direct disabled workers towards sickness presence. The results indicate that workplaces are not adapted to disabled workers in regard to their limitations.

DNA repair polymorphisms and treatment outcomes of patients with malignant mesothelioma treated with gemcitabine-platinum combination chemotherapy.

INTRODUCTION: Genetic polymorphisms that affect DNA repair capacity can modulate the efficacy and toxicity of cytotoxic agents. Therefore, the aim of our study was to evaluate the influence of genetic variability in DNA repair genes on treatment outcome in patients with malignant mesothelioma (MM) treated with gemcitabine-platinum combination chemotherapy. METHODS: In total, 109 patients with MM were genotyped for 10 polymorphisms in XRCC1, NBN, RAD51, and XRCC3 genes. The influence of selected polymorphisms on tumor response and occurrence of treatment-related toxicity was determined by logistic regression analysis, whereas their influence on survival was estimated by Cox proportional hazards model. RESULTS: There were no associations between the investigated polymorphisms and tumor response, but we observed a significant association between XRCC1 399Gln allele and reduced overall survival (hazards ratio = 1.70; 95% confidence interval [CI] 1.06-2.73; p = 0.028). Interaction between XRCC1 399Gln allele and C-reactive protein levels revealed that carriers of at least one XRCC1 399Gln allele with C-reactive protein levels above median had significantly shorter overall survival time compared with other patients (12.9 months versus 25.3 months, log-rank p < 0.001). We also observed an association between XRCC1 399Gln and lower frequency of leukopenia (odds ratio [OR] = 0.25; 95% CI 0.09-0.67; p = 0.006), neutropenia (OR = 0.24; 95% CI 0.09-0.68; p = 0.007), and thrombocytopenia (OR = 0.27; 95% CI 0.09-0.84; p = 0.024). In addition, NBN 3474A>C, XRCC3 -316A>G, and Thr241Met polymorphisms showed significant associations with treatment-related toxicity. CONCLUSIONS: Our results support the hypothesis that DNA repair gene polymorphisms, particularly XRCC1 Arg399Gln, may modify the response to gemcitabine-platinum combination chemotherapy and, for the first time, show this effect in patients with MM.

Soluble mesothelin-related peptides levels in patients with malignant mesothelioma.

Soluble mesothelin-related peptides (SMRP) are a potential tumor marker for malignant mesothelioma. The aim of this study was to determine the differences in SMRP levels in patients with malignant mesothelioma before treatment and in various responses to treatment and to investigate whether SMRP level could be useful in evaluating tumor response to treatment. The study included patients with malignant mesothelioma treated at the Institute of Oncology Ljubljana between March 2007 and December 2009. Blood samples were collected before treatment and/or in various responses to treatment. SMRP levels were determined using ELISA assay based upon a combination of two monoclonal antibodies. Mann-Whitney test was used to determine the differences in SMRP levels in various responses to treatment. Median SMRP was 2.80 nmol/L (range 0.00-34.80) before treatment, 0.00 nmol/L (range 0.00-0.00) in complete response, 0.48 nmol/L (range 0.00-4.40) in partial response, 1.65 nmol/L (range 0.00-20.71) in stable disease and 7.15 nmol/L (range 0.44-31.56) in progressive disease. Pre-treatment SMRP levels were significantly higher than in stable disease, partial response and complete response (p=0.006), as were SMRP levels in progressive disease compared to stable disease, partial response and complete response (p< 0.001). Our findings suggest that SMRP may be a useful tumor marker for detecting the progression of malignant mesothelioma and evaluating tumor response to treatment.

The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma.

OBJECTIVE: Identification of biomarkers that could predict gemcitabine efficacy and toxicity is a key issue in the development of individualized therapy. The aim of our study was to evaluate the influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma (MM). METHODS: In total, 107 patients with MM, treated with gemcitabine-platinum chemotherapy, were genotyped for 11 polymorphisms in deoxycytidine kinase, ribonucleotide reductase M1 (RRM1), and cytidine deaminase genes using KASPar assays. Binary logistic regression was used to evaluate the influence of selected polymorphisms on tumor response and occurrence of treatment-related toxicity, while their influence on survival was estimated by Cox proportional hazards model. A haplotype analysis was carried out to assess the combined effect of RRM1 polymorphisms. RESULTS: Deoxycytidine kinase and cytidine deaminase polymorphisms did not influence treatment outcome in patients with MM. In multivariable analysis, RRM1 2927A>C polymorphism significantly decreased overall survival probability [hazard ratio (HR)=2.02; 95% confidence interval (CI)=1.11-3.65; P=0.021]. Two promoter polymorphisms, RRM1 -524T>C and -37C>A, decreased the odds of nausea/vomiting grade≥2 occurrence [odds ratio (OR)=0.25; 95% CI=0.10-0.60; P=0.002 and OR=0.26; 95% CI=0.11-0.63; P=0.003, respectively]. RRM1 TTCCA haplotype was associated with worse tumor response (OR=16.67; 95% CI=2.38-100.00; P=0.004) and worse overall survival (HR=2.97; 95% CI=1.46-6.06; P=0.003) compared with the most frequent TTCAA haplotype, while TCACA haplotype influenced nausea/vomiting grade≥2 occurrence (OR=0.27; 95% CI=0.12-0.60; P=0.001). CONCLUSION: RRM1 polymorphisms as well as haplotypes showed an association with gemcitabine treatment efficacy and toxicity; therefore, they should be validated as potential markers for the prediction of clinical outcome in patients with MM.

Inducible nitric oxide synthase genetic polymorphism and risk of asbestosis.

Asbestos, a known occupational pollutant, may upregulate the activity of inducible nitric oxide synthase (iNOS) and thus the production of nitric oxide (NO). This study investigated whether iNOS (CCTTT)(n) polymorphism is associated with an increased asbestosis risk in exposed workers. The study cohort consisted of 262 cases with asbestosis and 265 controls with no asbestos-related disease. For each subject the cumulative asbestos exposure data were available. The number of CCTTT repeats was determined following PCR amplification of the iNOS promoter region. Logistic regression was performed to estimate asbestosis risk. The OR of asbestosis was 1.20 (95% CI = 0.85-1.69) for the LL genotype compared to the combined SL and SS genotypes and 1.26 (95% CI = 0.86-1.85) for the LL genotype compared to the SL genotype. The results of this study are borderline significant and suggest a possible role of iNOS (CCTTT)(n) polymorphism in the risk of asbestosis; however, further studies are needed.

Manganese and extracellular superoxide dismutase polymorphisms and risk for asbestosis.

Manganese and extracellular superoxide dismutases (SOD2 and SOD3) are part of the enzymatic defence against reactive oxygen species, which are involved in the pathogenesis of asbestosis. This study investigates whether SOD2Ala - 9Val and SOD3 Arg213Gly genetic polymorphisms represent risk factors for asbestosis in workers exposed to asbestos. The study included 262 cases with asbestosis and 265 controls with no asbestos-related disease. Cumulative asbestos exposure was calculated for each subject. A real-time PCR assay was introduced for genotyping. Logistic regression analysis was used to assess asbestosis risk. Asbestosis was associated with the homozygous SOD2 - 9Ala/Ala genotype (OR = 1.50, 95% CI 1.01-2.24), whereas the association for the SOD3 Arg/Gly genotype was not significant (OR = 1.63, 95% CI 0.62-4.27). The finding that the SOD2 - 9Ala/Ala genotype increases the risk for asbestosis indicates that, in addition to asbestos exposure, genetic factors may also have a significant influence on the development of asbestosis.

Asbestosis and catalase genetic polymorphism.

Catalase (CAT) is part of the enzymatic defense system against reactive oxygen species (ROS), known to be involved in the pathogenesis of asbestosis. This study investigates whether CAT -262 C>T genetic polymorphism influences the risk of asbestosis in workers occupationally exposed to asbestos.The nested case-control study included 262 cases with asbestosis and 265 controls with no asbestos-related disease. Data on cumulative asbestos exposure and smoking were available. A real-time PCR assay was introduced for genotyping CAT -262 C>T promoter polymorphism.A slightly elevated risk of asbestosis was observed in subjects with the CAT -262 TT genotype compared to others (OR=1.36, CI 0.70-2.62). This risk did not change substantially after adjustment by sex, age, and smoking, but the involvement of cumulative asbestos exposure changed the OR to 1.91 (CI 0.93-3.91). These findings indicate that the CAT -262 TT genotype may be slightly associated with an increased risk of asbestosis. No synergistic effect was found between cumulative asbestos exposure and the CAT -262 TT genotype, but cumulative asbestos exposure acted as a confounder. These results are an important contribution to understanding the interactions between genetic and environmental factors that may modify the risk of asbestosis.

Using different methods to assess the discomfort during car driving.

This study investigated the discomfort caused by car driving. Discomfort estimates were achieved by self-administered questionnaire, measured by different testing methods, and through the goniometry of principal angles. Data from a total of 200 non-professional drivers who fulfilled the questionnaire was analysed. 118 subjects were analysed by goniometry and 30 drivers were assessed using the OWAS (Ovaco orking Posture Analysis), RULA (Rapid Upper Limb Assessment), and CORLETT tests. The aim of this paper was to assess the appearance of the discomfort and to find some correlations between drivers' postures. Results suggest that different levels of discomfort are perceived in different body regions when driving cars. Differences appear mostly between the genders concerning the discomfort. With the questionnaire and the different estimation techniques, it is possible to identify 'at risk' drivers and ensure urgent attention when necessary. It can be concluded that the questionnare and the CORLETT test are good in predicting location of discomfort. TheB org CRI10scale is good indicator of the level of the discomfort, while OWAS and RULA can appraise the body posture to predict discomfort appearance. According to the goniometry data, the drivers posture could be one of the contributing factors in appearing of discomfort.

The influence of genetic polymorphisms of GSTP1 on the development of asbestosis.

OBJECTIVE: Genetic factors play an important role in the development of asbestosis. The aim of this study was to investigate whether genetic polymorphisms of glutathione S-transferase (GST) P1 represent a risk factor for this disease. METHODS: The study population included 262 workers with asbestosis and 265 matched controls. Information on cumulative asbestos exposure was available. A real-time PCR based on the 5' nuclease assay was designed for the analysis of GSTP1 Ile105Val and Ala114Val polymorphisms. RESULTS: Asbestosis was associated with GSTP1 genotype coding for an enzyme with high conjugation capacity versus genotypes resulting in intermediate and low enzyme activity (odds ratio = 1.49, confidence interval = 1.06-2.10). CONCLUSIONS: The key finding of the study was that GSTP1 genotype coding for an enzyme with high conjugation capacity significantly increases the risk of developing asbestosis.

Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis.

OBJECTIVE: In a nested case-control study, the authors investigated whether the deletion polymorphism of glutathione S-transferases GSTM1 and GSTT1 represents a risk factor for the development of asbestosis. METHODS: In total, 262 cases with asbestosis and 265 controls, selected from a cohort of 2080 workers occupationally exposed to asbestos, were genotyped for GSTM1 and GSTT1-null alleles. Cumulative exposure for each subject was available. RESULTS: Asbestosis was associated with cumulative exposure (odds ratio [OR]=3.21, confidence interval [CI] 2.43-4.23) and GSTT1-null genotype (OR=0.61, CI 0.40-0.94), but not with GSTM1-null genotype (OR=1.01, CI 0.71-1.43). The risk of GSTM1-null and GSTT1-null genotype for asbestosis did not change after adjustment by cumulative exposure, smoking, gender, and age. CONCLUSIONS: An important finding of this study is that GSTT1 gene deletion might have a protective effect on the development of asbestosis.