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/m(3)-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.

Occupational exposure and liver cancer in women: results of the Multicentre International Liver Tumour Study (MILTS).

The association of occupational variables and hepatocellular cancer (HCC) is discussed with particular reference to women, as little research has been undertaken on their behalf. This paper reports the results of an international case-control study concerning women and involves 317 cases of HCC and 1789 controls. Working in the chemical industry was shown to have only a marginally significant risk associated with HCC: adjusted odds ratio (OR) and 95% confidence interval 2.37 (1.04-5.41). Other non-significantly elevated ORs were observed in the pharmaceutical, plastics, PVC-producing, farming and butchery industries. Little consistency was found among the risk estimates for HCC, based on three different analytical approaches. None of the analyses showed a linear trend of risk with increasing duration of exposure. However, the numbers of exposed cases and controls were small for many of the occupations and therefore the study power and precision were low. We failed to find important and consistent evidence for a relationship between HCC in women and occupational variables. However, even weak evidence of occupational risk warrants careful consideration in future studies.

Occupational lung cancer risk for men in Germany: results from a pooled case-control study.

Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60).

Lung cancer and exposure to man-made vitreous fibers: results from a pooled case-control study in Germany.

BACKGROUND: To investigate the association between lung cancer and occupational exposure to man-made vitreous fibers (MMVF), a pooled analysis of two case-control studies was conducted in the years 1988-1994. METHODS: The case series consisted of 3498 males who were histologically or cytologically verified primary lung cancer cases. 3541 male population controls were drawn at random from the general population and matched to cases by sex, age, and place of residence. To examine the relationship between MMVF and lung cancer we asked all study subjects who worked for at least 6 months as construction and installation workers whether they ever installed or removed insulations and what kind of insulation material they used. RESULTS: Some 304 (8.7%) cases and 170 (4.8%) controls reported to have insulated with glass wool or mineral wool mats. Coded as ever/never exposed, the odds ratio was 1.48 (95% CI: 1.17-1.88), adjusted for smoking and asbestos. To be sure to exclude any confounding effect of asbestos, we tried to identify those cases and controls who insulated with glass wool or mineral wool mats only and never reported any asbestos exposure. For this group we calculated an odds ratio of 1.56 (95% CI: 0.92-2.65), after adjustment for smoking. An elevated risk was also estimated on the basis of an expert rating which was done for a subgroup of cases and controls. Ever exposure to MMVF (but not to asbestos) in this subgroup yielded an odds ratio of 1.30 (95% CI: 0.82-2.07). CONCLUSIONS: Our study provides some indication for an excess risk of man-made vitreous fibers. This result also persists after adjustment for smoking and asbestos.

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.

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.

Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon.

BACKGROUND: For unknown reasons, the age-standardized incidence of testicular cancer has shown a rapid increase in virtually all countries (mostly Western) studied. For populations with a sufficiently long period of cancer registration, this development can be traced back to the first half of this century. PURPOSE: By evaluating data from six countries with long periods of cancer registration (Denmark, Norway, Sweden, the former German Democratic Republic [East Germany], Finland, and Poland), we sought to determine whether the increase in testicular cancer risk follows a birth cohort pattern and, if so, to quantify and compare any birth cohort effects. METHODS: A total of 30,908 incident cases of testicular cancer, diagnosed from 1945 through 1989 in men who were 20-84 years of age, were identified in population-based cancer registries in the six countries. In addition to performing simple trend analyses, we fitted several Poisson regression models (with the explanatory variables age, time period [calendar time], and birth cohort) to the data. Individual models were estimated by the maximum likelihood method. RESULTS: The age-standardized incidence of testicular cancer was found to vary among the six populations and, on the basis of total registration data, increased annually at rates ranging from 2.3% (in Sweden) to 5.2% (in East Germany). A comparison of several regression models indicated that birth cohort was a stronger determinant of testicular cancer risk than was calendar time for all six populations. Within each population, little variation in testicular cancer risk was observed for men born between 1880 and 1920; thereafter, the risk began to increase. Among men born in Denmark, Norway, and Sweden between 1930 and 1945 (the period encompassing the Second World War), the increasing trend in risk was interrupted (i.e., a leveling in risk occurred). After 1945, an uninterrupted increase in risk was observed for all six populations. With men born around 1905 as the reference group, the relative risk of testicular cancer for those born around 1965 varied from 3.9 (95% confidence interval [CI] = 2.7-5.6) in Sweden to 11.4 (95% CI = 8.3-15.5) in East Germany. CONCLUSIONS AND IMPLICATIONS: The increasing trend in testicular cancer risk observed for these six populations follows a birth cohort pattern. This distinct risk pattern provides a framework for the identification of specific etiologic factors.

Multicentre international liver tumour study protocol of the case-control study on hepatocellular cancer.

Toxicological evidence has recently shown that cyproterone acetate (CPA) is associated with increased adduct formation in liver cell cultures that was interpreted as a possible sign for genotoxicity. Likewise, a few spontaneous reports of liver cancer associated to CPA were published. This led to an alert announced by the German Drug Regulators. One reason to design a case-control study on hepatocellular cancer (HCC) and oral contraceptives (OC's) use (and specific subtypes such as CPA-containing ones) was that other clinical or pharmacoepidemiological studies were not available which dealt with this suspicion. This idea got support from the fact that most of the earlier case-control studies on HCC and OC were small, did not sufficiently control for confounding by: hepatitis B and C, exposure at work, use of other potentially hepatotoxic drugs and also did not distinguish between different types of OC's. Objectives, hypotheses, methods used and subjects studied are described in this paper. The study began in six countries (Germany, United Kingdom, France, Italy, Spain, Greece) on 1 July 1994. It will be finished by the end of June 1996, and first results can be expected by the end of 1996 or early 1997.

[C-erbB-2, PCNA and histomorphologic factors in breast carcinoma after oral contraceptive use]. / C-erbB-2, PCNA und histomorphologische Faktoren beim Mammakarzinom nach Einnahme oraler Kontrazeptiva.

The influence of oral contraceptives (OC) on histomorphological and molecular biological prognostic factors was studied in 471 breast cancer patients. Differences in histological tumor type, histological grade, tumor size, lymph node status, hormonal receptor status, PCNA expression and c-erbB-2 protein overexpression were investigated in relation to the duration of OC use (< 5 years/ > or = 5 years) and the time since last use. A total of 297 (63%) patients had used oral contraceptives at some time in their life; 186 patients (39.5%) had used OC's for 5 years or more. There were no significant differences in the tumor characteristics investigated with respect to OC use in general. Neither long-term use at some time in their life nor long-term use until breast cancer diagnosis had an effect on histomorphological and molecular biological factors. Thus, steroid hormones contained in OC's had no direct effect on prognostic factors in breast cancer.

Patterns of cigarette sales and lung cancer mortality in some central and eastern European countries, 1960-1989.

BACKGROUND: Remarkable increases in lung cancer risk recently have been observed in the Central and Eastern European (CEE) area. This study examines the patterns of lung cancer mortality rates and cigarette sales in 1960-1989 in seven CEE countries with a total population of 97.5 million and 43,000 deaths from lung cancer in the last year under study. METHODS: Trends in cigarette sales and mortality rates from lung cancer in seven CEE countries were compared for the years 1960-1989. RESULTS: Among males, recent lung cancer death rates were the highest in Europe, and trends by country largely reflected the varied prevalence and duration of smoking in previous decades. For females, lung cancer mortality rates were much lower, although there were exponential rate increases. In the more recent birth cohorts, there were some declines in mortality rates among males, but not among females. CONCLUSIONS: The rising cigarette consumption through the 1960s, 1970s, and, in some countries, the 1980s is accompanied in most of the countries by rising lung cancer mortality rates for young adults. This increasing cigarette consumption will determine future trends in lung cancer, which will increase well beyond the turn of the century and will continue longer for females than for males. This outlook underlines the urgent need for comprehensive lung cancer prevention with the concerted control of smoking as a priority. The role of cofactors and their interaction with smoking deserve further exploration.

Prognostic value of proliferating cell nuclear antigen and c-erbB-2 compared with conventional histopathological factors in breast cancer.

Expression of proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein has been assessed in 471 women with breast cancer to evaluate their prognostic value as compared to conventional histopathological factors. In univariate analysis, high PCNA expression (> or = 20%) predicted a significantly worse survival in lymph-node-negative tumors (univariate P = 0.031). However, the effect disappeared in multivariate analysis and the histological grade remained the only independent factor for this group. Despite its close correlation to histological grade (P < 0.001), PCNA expression discriminated subsets with different survival within the heterogeneous group of moderately differentiated tumors (univariate P = 0.073, multivariate P = 0.075). PCNA expression was not found to be a significant prognostic factor in lymph-node-positive tumors, thus it was of limited value for breast cancer patients as a whole. c-erbB-2 protein overexpression was associated with a worse survival (univariate P = 0.019, multivariate P = 0.057) for the entire group of patients. The effect was mainly attributed to the significance of c-erbB-2 as an independent factor in lymph-node-positive (up to three nodes, multivariate P = 0.04; four or more nodes: multivariate P = 0.017) and large tumors (> 2 cm: multivariate P = 0.002). c-erbB-2 was without significance in lymph-node-negative patients. Though both factors might amplify the prognostic information for distinct patient subsets they do not achieve the strong prognostic value of conventional histopathological features in breast cancer.

Testicular cancer in nine northern European countries.

The incidence of testicular cancer was examined in the Nordic and Baltic countries, Poland and Germany by collaboration among 10 cancer registries. Population-based registers were used to analyze a total of 34,309 cases, diagnosed from the start of registration (varying from 1943 in Denmark to 1980 in Latvia and Lithuania) through 1989. An approximately 10-fold geographical variation was found in 1980, with the highest age-standardized incidence rate (7.8 per 10(5); world standard population) in Denmark and the lowest (0.9) in Lithuania. During the entire period of registration, incidence increased rapidly in all countries, by 2.3 to 3.4 per cent annually in the Nordic countries and by about 5 per cent in Poland and Germany; there was some evidence of a slower increase in Denmark and Poland after 1975. The rising trend was more pronounced for ages below 30. The age-specific incidence peaked in all countries at ages 25 to 34, but the geographical variation was considerable. Our data indicate that environmental influences on testicular cancer are strong. Exposure to causal factors mostly takes place early in life, shows substantial geographical variation, and increases over time, so that the age-standardized incidence doubles every 15 to 25 years. New aetiological hypotheses are needed to accommodate these salient features of the descriptive epidemiology, since risk factors considered so far cannot explain the observed pattern.

[Effect of oral contraceptives on the proliferative activity of breast cancer]. / Der Einfluss oraler Kontrazeptiva auf die Proliferationsaktivität des Mammakarzinoms.

In 471 breast cancer patients the possible influence of an antecedent oral contraceptive (OC) use on proliferative activity (PCNA-expression) of mammary carcinomas was investigated. PCNA-expression (Proliferating Cell Nuclear Antigen) was immunohistochemically assessed using formalin-fixed, paraffin-embedded tissue. PCNA-expression discriminated tumors of low (< 20%) and increased (> or = 20%) proliferative fractions. 297 (63%) patients had ever used OCs and 202 (43%) of them were long-term users (> or = 49 months). Age adjusted proliferative fractions showed no statistically significant differences dependent on duration of OC use (never, 1-48 months, > or = 49 months), despite a slightly higher frequency of tumors with an increased PCNA-expression in ever users of OCs (p = 0.125).

C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk.

The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.