A database of exposures in the rubber manufacturing industry: design and quality control

The concerted action EXASRUB was initiated to create a database management system for information on occupational hygiene measurements that could be used to develop exposure models in the European rubber manufacturing industry. Quality of coding was assessed by calculating percentages of agreement and Cohen's kappa statistics (kappa) for an intra- and inter-centre recoding of randomly selected subsets of the measurements. In a 6-month period, 59 609 measurements from 523 surveys in 333 factories from as early as 1956 to 2003 were coded. The database consists primarily of measurements of N-nitrosamines (36%), rubber dust (23%), solvents (14%) and rubber fumes (10%). Coding of epidemiologically relevant information was done consistently with inter-centre kappa between 0.86 and 1.00. For occupational hygiene information, values of kappa were estimated to be between 0.67 and 1.00. The proposed method resulted in a large quantity of exposure measurements with auxiliary information of varying completeness and quality. Analyses showed that coding of epidemiologically relevant information in such a multi-centre, multi-country study was coded consistently. Larger errors however, occurred in coding of occupational hygiene information. This was primarily caused by lack of information in the primary records of measurements, emphasizing the importance of having a universal system in place to collect and store measurement information by occupational hygienists for future use.     

Lung cancer risk and occupational exposure to meat and live animals

An increased risk of lung cancer has been reported for butchers and meat workers in several cohort studies, although confounding from tobacco smoking could not be ruled out in any of these studies. These exposures, as well as a potential risk associated with contact with live animals, are addressed here in a large case-control study with full adjustment for smoking. More than 5,900 subjects were included in a case-control study conducted in 7 European countries. For each job they employed local experts who assessed the exposure to a number of occupational agents, including (i) meat aerosols and (ii) live animals, on the basis of detailed occupational questionnaires. Information on tobacco consumption and other risk factors was also collected. A small increased risk of lung cancer was observed with exposure to meat aerosols, after adjusting for smoking, (odds ratio (OR)=1.27, 95% confidence interval (CI): 0.92, 1.75), which was most apparent for the upper tertile of cumulative exposure (OR=1.73, 95% CI: 1.03, 2.92). A similar overall effect was observed for exposure to live animals, with an increased risk observed for a high frequency of exposure, (OR=1.69, 95% CI: 1.21, 2.36) and a high intensity of exposure, (OR=1.85, 95% CI: 1.16, 2.94), with significant trends for increasing frequency (p=0.012), intensity (p=0.015) and cumulative exposure (p=0.024). In conclusion, this study provides evidence for an association between exposure to meat aerosols and lung cancer apparent in the highest tertile of exposure. The authors identified a more consistent association with exposure to live animals.     

Folate-related genes and the risk of tobacco-related cancers in Central Europe

Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.     

Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways.

The DNA repair systems maintain the integrity of the human genome and cell cycle checkpoints are a critical component of the cellular response to DNA damage. We hypothesized that genetic variants in DNA repair and cell cycle control pathways will influence the predisposition to lung cancer, and studied 27 variants in 17 DNA repair enzymes and 10 variants in eight cell cycle control genes in 1,604 lung cancer patients and 2,053 controls. To improve the estimation of risks for specific variants, we applied a Bayesian approach in which we allowed the prior knowledge regarding the evolutionary biology and physicochemical properties of the variant to be incorporated into the hierarchical model. Based on the estimation from the hierarchical modeling, subjects who carried OGG1 326C/326C homozygotes, MGMT 143V or 178R, and CHEK2 157I had an odds ratio of lung cancer equal to 1.45 [95% confidence interval (95% CI), 1.05-2.00], 1.18 (95% CI, 1.01-1.40), and 1.58 (95% CI, 1.14-2.17). The association of CHEK2 157I seems to be overestimated in the conventional analysis. Nevertheless, this association seems to be robust in the hierarchical modeling. None of the pathways seem to have a prominent effect. In general, our study supports the notion that sequence variation may explain at least some of the variation of inherited susceptibility. In particular, further investigation of OGG1, MGMT, and CHEK2 focusing on the genetic regions where the present markers are located or the haplotype blocks tightly linked with these markers might be warranted.     

Family history and lung cancer risk: international multicentre case–control study in Eastern and Central Europe and meta-analyses

Lung cancer is the most common neoplastic disease in Eastern and Central Europe. The role of hereditary factors in lung carcinogenesis is not fully understood. Family history (FH) of lung cancer and other tobacco-related cancers might be a strong predictor of the lung cancer risk. We investigated family history of cancer among first-degree relatives of 2,861 patients with lung cancer and 3,118 controls from the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and United Kingdom within the IARC Multicenter Case–Control Study. Odds ratios (ORs) and 95% CI were calculated using logistic regression, adjusting for age, gender, study center, education, tobacco smoking, and number of first-degree relatives. In addition, we conducted a meta-analysis of 41 studies on FH of cancer and lung cancer risk. Positive FH of lung cancer increased risk of lung cancer with OR of 1.63 (95%CI: 1.31–2.01), and having two or more affected relatives with lung cancer further increased the risk of lung cancer with OR 3.60 (95%CI: 1.56–8.31). Among subjects aged less than 50, the OR for FH of lung cancer was 2.08 (95%CI: 1.18–3.63). The associations were generally stronger for squamous cell carcinoma and large cell carcinoma subtypes. Heterogeneity in results was not found with respect to smoking status and gender. A significant association was not observed for FH of other smoking-related tumors. The results of meta-analysis were consistent with that of our study with regard to young onset, non-smokers and histology. FH of lung cancer is a predictor of an increased risk of lung cancer, especially in subjects aged less than 50.     

Occupational diseases in Poland, 2001

The Central Register of Occupational Diseases keeps the records of all reported and certified occupational diseases in Poland. In this paper the incidence of occupational diseases in Poland in 2001 is discussed on the basis of the data provided by the Register. The changes in the incidence pattern over the recent 30 years are also shown. In 2001, 6,007 cases of occupational diseases were registered, with the incidence rate of 63.2 per 100,000 employees. The highest incidence rates were noted for seven categories of diseases: the vocal organ diseases, noise-induced hearing loss, pneumoconioses, contagious and invasive diseases, dermatoses, chronic diseases of bronchi, and vibration syndrome. Altogether these diseases covered 5,239 cases (87.2% of all registered cases). Mining and quarrying, agriculture, hunting and forestry, education, health and social works were the economy activities with the highest incidence of occupational diseases. The majority of occupational diseases (93.9%) have developed after a long-term (over 10 years) exposure to particular harmful factors. As much as 58.5% of cases were recorded in males. The predominant occupational diseases in males were occupational hearing lesions, while in females chronic vocal organ diseases, most common in teachers, were most frequently recognized. In Poland, the diseases of the vocal organ poses a serious problem from the medical and socio-economic points of view. These pathologies show the highest dynamics of the incidence among all registered occupational diseases. Over the last five years the vocal organ diseases have moved upwards to the top in the ranking, both with respect to the number of cases and the incidence rate. Since 1998, the incidence of occupational diseases has been continuously showing a downward tendency. Four categories of occupational diseases have accounted mostly for this decline: noise-induced hearing loss, chronic diseases of vocal organ, contagious and invasive diseases, and dermatoses (a decrease by 64%, 54%, 40%, and 51%, respectively). The decreased incidence has been also noted for "classical pathologies": chronic poisonings, pneumoconioses and vibration syndrome. At least three most important explanatory factors have to be pointed out: a) the decrease in employment and liquidation of industrial plants with the highest health risk; b) the modernization of plants and improvement of working conditions: and c) effective prevention.     

Mortality study of workers compensated for asbestosis in Poland, 1970-1997

The aim of the study was to assess the risk of asbestos-related malignancies among persons with diagnosed asbestosis. The study covered a cohort composed of 907 men and 490 women afflicted by asbestosis, diagnosed is 1970-1997. The follow-up of the cohort continued until 31 December 1999. In all, 421 deaths were registered and causes of death were retrieved for 93.3% of the deceased. A significantly increased mortality was observed both in the male 1300 deaths; SMR = 127; 95%CI: 113-142) and female (121 deaths, SMR = 150; 95%CI: 124-179) cohorts. The elevated number of deaths in the male and female cohorts were noted mainly due to respiratory diseases (men: 42 deaths; SMR = 344; 95%CI: 248-465; women: 20 deaths, SMR = 789; 95%CI: 482-1219) malignant neoplasms (men: 91 deaths, SMR = 146; 95%CI: 118-179; women: 34 deaths, SMR = 159; 95%CI: 110-222), including lung cancer (men: 39 deaths, SMR = 168; 95% CI: 119-230; women: 13 deaths, SMR = 621; 95%CI: 331-1062) and pleural mesothelioma (men: 3 deaths, SMR = 2680; 95%CI: 553-7832; women: 3 deaths, SMR = 7207; 95%CI: 1031-14612). Taking into account a cumulative dose of fibers, it was found that a significantly increased mortality from lung cancer and pleural mesothelioma applied to persons exposed to a dose above 25 f-y/ml. The results indicate that persons with asbestosis are at higher risk of developing malignant neoplasms, especially lung cancer and mesothelioma.