Jan Gromiec

Occupational Trichloroethylene Exposure and Renal Carcinoma Risk: Evidence of Genetic Susceptibility by Reductive Metabolism Gene Variants

Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >or=1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.

Assessing exposure misclassification by expert assessment in multicenter occupational studies

Background: In a multicenter case-control study of lung cancer in central and eastern Europe and in Liverpool, exposure to occupational agents was assessed by teams of local experts. We performed an interteam agreement study to estimate the levels of exposure misclassification and the expected attenuation of the risk estimate. Methods: Eight teams of experts and a reference rater assessed exposure to 70 putative lung carcinogens for 19 jobs. Agreement among teams was calculated through Cohen’s kappa, sensitivity, and specificity. Results: Each team showed an overall fair to good agreement with the reference (kappa between 0.53 and 0.64). The agreement among teams in the presence of exposure was excellent for 9 agents, fair to good for 16, and poor for 29. For all agents the specificity was high (average 0.94), although sensitivity varied considerably. Conclusions: This study of expert exposure assessment showed a small range in reliability among teams of experts, but large differences among agents. This paper presents the range in levels of misclassification that can be expected using experts for assessing occupational exposure to different agents, and the attenuation of the odds ratio that can be expected to result from this misclassification.

Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms

This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.

Renal cancer risk and occupational exposure to polycyclic aromatic hydrocarbons and plastics

Objective: To investigate whether occupational exposure to polycyclic aromatic hydrocarbons and certain plastic monomers increased renal cell carcinoma (RCC) risk. Methods: Unconditional logistic regression was used to calculate RCC risk in relation to exposure. Results: No association between RCC risk and having ever been occupationally exposed to any polycyclic aromatic hydrocarbons or plastics was observed. Duration of exposure and average exposure also showed no association with risk. Suggestive positive associations between RCC risk and cumulative exposure to styrene (P-trend = 0.02) and acrylonitrile (P-trend = 0.06) were found. Cumulative exposure to petroleum/gasoline engine emissions was inversely associated with risk (P-trend = 0.02). Conclusions: Results indicate a possible association between occupational styrene and acrylonitrile exposure and RCC risk. Additional studies are needed to replicate findings, as this is the first time these associations have been reported and they may be due to chance.

Evaluation of Occupational Exposure to Toxic Metals Released in the Process of Aluminum Welding

The objective of this study was to evaluate occupational exposure to welding fumes and its elements on aluminum welders in Polish industry. The study included 52 MIG/Al fume samples and 18 TIG/Al samples in 3 plants. Air samples were collected in the breathing zone of welders (total and respirable dust). Dust concentration was determined gravimetrically, and the elements in the collected dust were determined by AAS. Mean time-weighted average (TWA) concentrations of the welding dusts/fumes and their components in the breathing zone obtained for different welding processes were, in mg/m3: MIG/Al fumes mean 6.0 (0.8-17.8), Al 2.1 (0.1-7.7), Mg 0.2 (< 0.1-0.9), Mn 0.014 (0.002-0.049), Cu 0.011 (0.002-0.092), Zn 0.016 (0.002-0.14), Pb 0.009 (0.005-0.025), Cr 0.003 (0.002-0.007), and TIG/Al fumes 0.7 (0.3-1.4), Al 0.17 (0.07-0.50). A correlation has been found between the concentration of the main components and the fume/dust concentrations in MIG/Al and TIG/Al fumes. Mean percentages of the individual components in MIG/Al fumes/dusts were Al: 30 (9-56) percent; Mg: 3 (1-5.6) percent; Mn: 0.2 (0.1-0.3) percent; Cu: 0.2 (< 0.1-1.8) percent; Zn: 0.2 (< 0.1-0.8) percent; Pb: 0.2 (< 0.1-1) percent; Cr: < 0.1 percent. The proportion of the respirable fraction in the fumes and their constituents varied between 10 percent and 100 percent. The results showed that MIG/Al fumes concentration was 1.2 times higher than the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV), and the index of the combined exposure to the determined agents was 2.3 (0.4-8.0), mostly because of high Al2O3 contribution. The background concentrations of the components (ca. 5-10 times lower than those in the breathing zone of the welders) did not exceed the Polish MAC value. The elemental composition of total and respirable fume/dust may differ considerably depending on welding methods, the nature of welding-related operations, and work environment conditions.

Occupational exposure to organic solvents and breast cancer in women

Background Although studies in rodents suggest possible associations between exposure to organic solvents and breast cancer, the evidence in humans is limited. Methods We evaluated job histories of 2383 incident breast cancer cases diagnosed during 2000–2003, and 2502 controls who participated in a large population-based case-control study in Poland. Industrial hygienists reviewed occupational histories and developed exposure metrics for total organic solvents and benzene. Unconditional logistic regression analyses estimated ORs and 95% CIs as the measure of association with breast cancer, controlling for breast cancer risk factors. Stratified analyses examined the potential modification by known breast cancer risk factors. Associations were also evaluated by oestrogen and progesterone receptor status and by other clinical characteristics of the tumours using polytomous regression analyses. Results Women who ever worked at jobs with organic solvents exposure had a small, non-significant increase in breast cancer risk (OR=1.16; 95% CI 0.99 to 1.4). A significant association was present for oestrogen receptor- and progesterone receptor-negative tumours (OR 1.40; 95% CI 1.1 to 1.8), but there was no association with tumours with both positive receptors (OR 0.97; 95% CI 0.8 to 1.2 (p heterogeneity: 0.008)). We did not observe trends with increasing level of exposure. Known breast cancer risk factors did not modify the association between organic solvents and breast cancer risk. No association with breast cancer was found for benzene exposure (OR 1.00; 95% CI 0.8 to 1.3). Conclusion Our study provides weak evidence for a possible association between occupational exposure to organic solvents as a class and breast cancer risk. The association might be limited to hormone receptor-negative tumours.

Occupational exposure to dusts and risk of renal cell carcinoma

Background:Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case–control study.Methods:General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression.Results:Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1–3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2–5.1), and brick dust (OR: 1.5; 95% CI: 1.0–2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed.Conclusion:Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings.

Elaboration of a quantitative job‐exposure matrix for historical exposure to airborne exposures in the Polish rubber industry

BACKGROUND A job-exposure matrix (JEM) for inhalable aerosols, aromatic amines, and cyclohexane soluble matter (CSM) was elaborated based on measurements collected routinely between 1981 and 1996. METHODS The data were grouped based on similarities in exposure levels and time trends in different departments, and were analyzed using smoothing splines and mixed effects models. RESULTS Although higher than in western European countries, inhalable aerosol exposure decreased after changes in production volume and implementation of exposure reduction measures in mid-1980s. Aromatic amines concentrations first increased following the factorys production volume, but subsequently decreased in more recent years. CSM concentrations were uniformly distributed between departments. CONCLUSIONS This JEM provides an overview of historical exposure levels in a large Polish rubber factory and will enable estimation of lifetime exposure for individual workers in a Polish rubber workers cohort and further investigation of the associations between specific exposures and cancer risk.