Matthias Möhner

Lung cancer risk in male workers occupationally exposed to diesel motor emissions in Germany.

BACKGROUND Although in several epidemiological studies exposure to diesel motor emissions (DME) shows an elevated lung cancer risk, it is still controversial whether DME is a human carcinogen. METHODS In a pooled analysis of two case-control studies on lung cancer in Germany a total of 3498 male cases with histologically or cytologically ascertained lung cancer and 3541 male population controls were included. Information about lifelong occupational and smoking history was obtained by questionnaire. Drivers of lorries, buses, taxies, diesel locomotives and forklift trucks, bulldozers, graders, excavators, and tractors, were considered as exposed to DME and their cumulative exposure was estimated. All odds ratios were adjusted for smoking and asbestos exposure. RESULTS The evaluation of lung cancer risk for all jobs with DME-exposure combined showed an odds ratio of OR=1.43 (95%-CI: 1.23-1.67). Most pronounced was the increase in lung cancer risk in heavy equipment operators (OR=2. 31 95%-CI: 1.44-3.70). The risk of tractor drivers increased with length of employment and reached statistical significance for exposures longer than 30 years (OR=6.81, 95%-CI: 1.17-39.51). The group of professional drivers (e.g., trucks, buses, and taxies), showed an increased risk only in West Germany (OR=1.44, 95%-CI: 1. 18-1.76), but not in East Germany (OR=0.83, 95%-CI: 0.60-1.14). DME-exposure in other traffic related jobs (e.g., diesel engine locomotive drivers, switchmen, forklift operators) was associated with an odds ratio of OR=1.53 (95%-CI: 1.04-2.24). CONCLUSIONS The study provides further evidence that occupational exposure to diesel motor emissions is associated with an increased lung cancer risk.

Occupational risk factors for lung cancer in women: Results of a case‐control study in Germany

BACKGROUND To investigate the association between lung cancer and occupational factors in women. METHODS Six hundred eighty-six women with lung cancer and 712 controls matched for age and region were interviewed to gather occupational histories and information about other risk factors and confounders. Odds ratios (OR) and 95%-confidence intervals (CI) were calculated. RESULTS There were 11 cases and 2 controls who reported occupational asbestos exposure. Significantly elevated risks (P < 0.05, smoking-adjusted), were observed in the following industries: chemical, oil (OR 3.7), pottery, glass (OR 2.5), engine, vehicle building (OR 2.2), paper, wood, print (OR 1.9), cleaning service, hairdressing, housekeeping, waste disposal (OR 1.5); and occupations: assemblers, unskilled metal workers (OR 2.5), stock clerks, etc. (OR 1.6), restaurant owners and hoteliers (OR 2.7), as well as waitresses and travel attendants (OR 2.6). CONCLUSIONS The study provides evidence that both occupations previously observed as hazardous in males, and occupations of particular significance for women only, play a role in the risk of lung cancer in women.

Solvent exposure and malignant lymphoma : a population-based case-control study in Germany

AimsTo analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study.MethodsMale and female patients with malignant lymphoma (n = 710) between 18 and 80 years of age were prospectively recruited in six study regions in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/Gütersloh, and Munich). For each newly recruited lymphoma case, a gender, region and age-matched (± 1 year of birth) population control was drawn from the population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least one year. On the basis of job task-specific supplementary questionnaires, a trained occupational physician assessed the exposure to chlorinated hydrocarbons (trichloroethylene, tetrachloroethylene, dichloromethane, carbon tetrachloride) and aromatic hydrocarbons (benzene, toluene, xylene, styrene). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking (in pack years) and alcohol consumption. To increase the statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis.ResultsWe observed a statistically significant association between high exposure to chlorinated hydrocarbons and malignant lymphoma (Odds ratio = 2.1; 95% confidence interval 1.1–4.3). In the analysis of lymphoma subentities, a pronounced risk elevation was found for follicular lymphoma and marginal zone lymphoma. When specific substances were considered, the association between trichloroethylene and malignant lymphoma was of borderline statistical significance. Aromatic hydrocarbons were not significantly associated with the lymphoma diagnosis.ConclusionIn accordance with the literature, this data point to a potential etiologic role of chlorinated hydrocarbons (particularly trichloroethylene) and malignant lymphoma. Chlorinated hydrocarbons might affect specific lymphoma subentities differentially. Our study does not support a strong association between aromatic hydrocarbons (benzene, toluene, xylene, or styrene) and the diagnosis of a malignant lymphoma.

Occupational and diagnostic exposure to ionizing radiation and leukemia risk among German uranium miners.

Lung cancer is a well-known effect of radon exposure in uranium mines. However, little is known about the induction of leukemia by radiation exposure in mines. Moreover, miners usually have occupational medical checkup programs that include chest x-ray examinations. Therefore, the aim of the present study was to re-examine leukemia risk among miners, taking into account exposure to x rays for diagnostic purposes. The data used were from a previously analyzed individually matched case-control study of former uranium miners in East Germany with 377 cases and 980 controls. Additionally, data on x-ray examinations were taken from medical records for most of the subjects. Finally, the absorbed dose to red bone marrow was calculated considering both occupational and diagnostic exposures. Using conditional logistic regression models, a moderately but not statistically significant elevated risk was seen in the dose category above 200 mGy for the combined dose from both sources [odds ratio (OR) = 1.33, 90% confidence interval (CI): (0.82–2.14)]. Ignoring the dose accumulated in the recent 20 y, the risk in the highest dose category (>105 mGy) was higher [OR = 1.77, 90% CI: (1.06–2.95)]. Ignoring diagnostic exposure yielded similar results. For the highest dose category (absorbed dose lagged by 20 y) the risk was more than doubled [OR = 2.64, 90% CI: (1.60–4.35)].

Chronic obstructive pulmonary disease and longitudinal changes in pulmonary function due to occupational exposure to respirable quartz

Objectives The present study sought to examine the long-term effects of exposure to respirable quartz on pulmonary function with particular focus on chronic obstructive pulmonary disease (COPD). Methods The study is based on the Wismut cohort of former uranium miners. Spirometric data were ascertained together with quantitative estimates of cumulative exposure to respirable quartz for each of 1421 study subjects born between 1954 and 1956. The case definition for COPD is based on the criteria of the Global Initiative for Chronic Obstructive Lung Disease. Linear mixed regression models were fitted to identify significant determinants of longitudinal changes in lung function parameters. Results An average of five spirometries were available for each miner. It was shown that cumulative exposure to 1 mg/m3-year respirable quartz leads, on average, to a relative reduction in forced expiratory volume in 1 s/ orced vital capacity (FEV1/FVC) of 2.75% (p<0.001). A nested case–control approach demonstrated that the risk for COPD stage I increases with increasing cumulative exposure to respirable quartz (OR 1.81 per 1 mg/m3-year). Conclusions This paper adds further evidence on the long-term effects of exposure to respirable quartz, which include a decline in pulmonary function parameters and an increase in the incidence of COPD.

Major histopathological patterns of lung cancer related to arsenic exposure in German uranium miners.

ObjectiveThe mechanisms of action of arsenic in the development of lung cancer are still not yet elucidated. Considering the relationship between arsenic and squamous cell carcinomas of the skin, we hypothesized that arsenic exposure may be more closely associated with squamous cell carcinoma of the lung.MethodsA comprehensive histopathological database and a detailed job-exposure matrix developed for former German uranium miners with exposure to arsenic, radon, and quartz were analyzed to quantitatively assess the effect of arsenic regarding cell type of lung cancer. The distributions of major lung cancer cell types in 1,786 German uranium miners were associated with levels of arsenic exposure under control for the other lung carcinogens. To evaluate the arsenic effects in association with a frequent occupational lung disease in miners stratification by silicosis was performed.ResultsThere was an arsenic-related increase of the proportion of squamous cell carcinoma of the lung but restricted to miners without silicosis. The increase was found at all levels of co-exposure to radon and quartz dust. In miners with silicosis, the proportion of adenocarcinoma increased with rising arsenic exposure. Arsenic exposure was associated with non-small cell lung cancer. Silicosis turned out as major determinant of the cell type related with arsenic.ConclusionThese results indicate a cell type characteristic effect of arsenic in the development of lung cancer.

Predicted number of lung cancer cases in Germany among former uranium miners of the Wismut

Between 1946-1990, the Wismut-Company in the former German Democratic Republic was the leading producer of uranium for the Soviet union. After the German reunification, a central welfare system for uranium miners of the Wismut Zentrale Betreuung Wismut (ZeBWiS) was initiated by the Hauptverband der Berufsgenossenschaften in 1992, and a data base of exposed employees was established. In spring 1993, data regarding 95,000 exposed persons were available from Saxony, but none from Thuringia. A sample of 3,654 persons was drawn. For 3,128 of them the working history at the Wismut could be reconstructed. Having established the age distribution and taking into account mortality of other causes, the expected age-specific mortality rates of lung cancer were calculated. Statistical risk models were applied. Assuming that for Saxony about 156,000 workers were exposed in underground mining and/or uranium processing, a total (past and future) of about 7,000-25,000 excess lung cancer cases are estimated to be due to exposure to radon and its progeny. From 1995 onwards about 1,300-4,800 additional cases are predicted in the population of exposed former Wismut workers in Saxony. The peak incidence was reached between 1985-1991. No prognosis for Thuringia can be given so far.

Silica dust, radon and death from non-malignant respiratory diseases in German uranium miners

Objective To quantify the relationship between death from non-malignant respiratory diseases (NMRD) and exposure to silica dust or radon in a cohort of 58 690 former German uranium miners. Methods In the follow-up period from 1946 to 2008, a total of 2336 underlying deaths from NMRDs occurred, including 715 deaths from chronic obstructive pulmonary diseases (COPD) and 975 deaths from silicosis or other pneumoconiosis. Exposure to respirable crystalline silica and radon was individually assessed by means of a comprehensive job-exposure matrix. Risk analyses were based on a linear Poisson regression model with the baseline stratified by age, calendar year and duration of employment. Results There was no increase in risk of death from COPDs or any other NMRDs in relation to cumulative exposure to silica (mean=5.9, max=56 mg/m3-years), except in the group of deaths from silicosis or other pneumoconiosis. Here, a strong non-linear increase in risk was observed. Cumulative radon exposure (mean=280; max=3224 Working Level Months) was not related to death from COPDs or any other NMRDs. Conclusions The present findings do not indicate a relationship between mortality from COPD with silica dust or radon. However, validity of cause of death and lack of control for smoking remain potential sources of bias.

IONIZING RADIATION AND RISK OF LARYNGEAL CANCER AMONG GERMAN URANIUM MINERS

Today it is uncontested that uranium miners are at increased risk of lung cancer, primarily owing to their exposure to radon. Whether they are also at an increased risk of cancer at other sites, especially in the respiratory tract, remains under discussion. The aim of the present study was to examine the laryngeal cancer risk among uranium miners. An individually matched case-control study of former uranium miners in East Germany was conducted, including 554 cases and 929 controls. Using conditional logistic regression models, a dose-response relationship between the risk of developing a laryngeal cancer and exposure to radon progeny could not be confirmed. Even in miners with a cumulative exposure of at least 1,000 WLM, only a slightly elevated risk could be observed of OR = 1.13 (0.75–1.70)95%. The study does not support the hypothesis of an association between exposure to short-lived radon progeny and laryngeal cancer risk. Moreover, signs are emerging that smoking could explain the moderate excess in laryngeal cancer cases observed in some miner cohorts.

A critical review of the relationship between occupational exposure to diesel emissions and lung cancer risk

Abstract In 2012, a working group of the International Agency for Research on Cancer classified diesel exhaust (DE) as a human carcinogen (Group 1). This decision was primarily based on the findings of the Diesel Exhaust in Miners Study (DEMS). The disparity between the results of various methodological approaches applied to the DEMS led to several critical commentaries. An expert panel was subsequently set up by the Health Effects Institute to evaluate the DEMS results, together with a large study in the trucking industry. The panel concluded that both studies provided a useful basis for quantitative risk assessments (QRAs) of DE exposure. However, the results of both studies were non-definitive as the studies suffer from several methodological shortcomings. We conducted a critical review of the studies used by the International Agency for Research on Cancer (IARC) working group to evaluate the relationship between DE and lung cancer. The aim was to assess whether the available studies support the statement of a causal relationship and, secondarily if they could be used for QRA. Our review highlights several methodological flaws in the studies, amongst them overadjustment bias, selection bias, and confounding bias. The conclusion from our review is that the currently published studies provide little evidence for a definite causal link between DE exposure and lung cancer risk. Based on two studies in miners, the DEMS and the German Potash Miners study, QRA may be conducted. However, the DEMS data should be reanalyzed in advance to avoid bias that affects the presently published risk estimates.