Cancer incidence in Swedish oil refinery workers exposed to benzene.

BACKGROUND: Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers' exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma. AIM: The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries. METHODS: Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35-47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. RESULTS: In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95-1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18-4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1-31.1). DISCUSSION: The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure. CONCLUSION: The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.

Silica dust and sarcoidosis in Swedish construction workers.

BACKGROUND: The aetiology of sarcoidosis is not well established. In previous studies, smoking has been negatively associated with sarcoidosis and there are some indications of an association between exposure to silica dust and sarcoidosis. AIMS: To study the risk of sarcoidosis in relation to silica dust exposure. METHODS: A longitudinal cohort of construction workers linked with a registry of Swedish inpatient diagnoses. Workers were designated as exposed or unexposed to silica based on job titles in a job-exposure matrix. The relative risk (RR) was analysed with Poisson regression adjusting for age and smoking. RESULTS: We identified 371 cases of sarcoidosis among 297 917 male workers. There was an increased risk of sarcoidosis in the medium- to high-exposure group [RR 1.83 (95% confidence interval {CI} 1.14-2.95)]. A stratified analysis according to smoking showed that ever-smoking workers had an increased risk of sarcoidosis if highly exposed to silica dust [RR 2.44 (95% CI 1.37-4.33)] compared to non-exposed ever-smokers. The risk of non-smokers highly exposed to silica was not significantly increased [RR 1.07 (95% CI 0.72-1.58)] compared to non-exposed non-smokers. CONCLUSION: The study indicates an increased risk of developing sarcoidosis in ever-smoking men exposed to silica.

Patient-reported signs of dampness at home may be a risk factor for chronic rhinosinusitis: A cross-sectional study.

BACKGROUND: An association between dampness at home and respiratory conditions has been convincingly demonstrated in children. Fewer studies have been performed in adults, and data are lacking for chronic rhinosinusitis (CRS). With a prevalence of 10.9% in Europe, CRS imposes a significant burden on quality of life, as well as economy. OBJECTIVE: Our aim was to study CRS and other respiratory conditions in relation to dampness at home in a representative sample of adults. METHODS: The Swedish GA2 LEN questionnaire was answered by 26 577 adults (16-75 years) and included questions on respiratory symptoms, smoking, education and environmental exposure. CRS was defined according to the EP3 OS criteria. Dampness was defined as reporting water damage, floor dampness or visible moulds in the home during the last 12 months. The dampness score was ranked from 0 to 3, counting the number of signs of dampness reported. RESULTS: Dampness at home was reported by 11.3% and was independently related to respiratory conditions after adjustment for demographic and socio-economic factors and smoking: CRS odds ratio (OR) 1.71; allergic rhinitis OR 1.24; current asthma OR 1.21; wheeze OR 1.37; nocturnal dyspnoea OR 1.80; nocturnal coughing OR 1.34; and chronic bronchitis OR 1.64. The risk of CRS and most of the other respiratory conditions was further elevated in subjects reporting multiple signs of dampness. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated an independent association between dampness at home and CRS in adults. The high burden of this and the other respiratory conditions studied is a strong argument in favour of countering indoor dampness by improving building standards.

Asbestos exposure and the risk of sinonasal cancer.

BACKGROUND: While the increased risk of lung cancer and mesothelioma is well established, the relationship between exposure to asbestos dust and sinonasal cancer is less clear. AIMS: To study the risk of sinonasal cancer in relation to asbestos dust exposure. METHODS: A retrospective cohort study of construction workers, linked to the Swedish Cancer Registry. Participants were classified into four exposure groups; heavy, medium, low or very low exposure to asbestos, according to the incidence of pleural mesothelioma in their occupational group. Standardized incidence ratios (SIRs) and relative risks (RRs) were analysed, adjusted for age and smoking habits. The risks of adenocarcinoma and squamous cell carcinoma were investigated separately. RESULTS: Among the 280222 subjects, there was no increased risk of sinonasal cancer compared to the general population [SIR 0.85, 95% confidence interval (CI) 0.68-1.03], or any dose-response relationship with exposure to asbestos. The highest RR was found in the low exposure group (RR 1.25, 95% CI 0.69-2.28) and the lowest RR was found in the group with the highest exposure to asbestos (RR 0.71, 95% CI 0.33-1.53). No significantly increased risk or dose-response association could be found for adenocarcinoma or squamous cell carcinoma when analysed separately. CONCLUSIONS: This study did not find an increased risk of developing sinonasal cancer after asbestos exposure.

Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.

Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.

Vehicle exhaust outside the home and onset of asthma among adults.

Few studies have investigated the relationship between vehicle exhaust and the new onset of asthma among adults. The aim of the present prospective cohort study was to investigate the relationship between the cumulative incidence of asthma and onset of asthma among adults and vehicle exhaust concentrations at home. Participants from three Swedish cities included in the Respiratory Health in Northern Europe cohort constituted the study population. Exposure at each participant's home was calculated using dispersion models. We also used <50 m distance to nearest major road as a more simple indicator of exposure. The adjusted model included 3,609 participants, of which 107 were classified as onset cases and 55 as true incident cases of asthma. There was a positive association between asthma onset (odds ratio (OR) per 10 microg x m(-3) 1.46, 95% confidence interval (CI) 1.07-1.99) and incident asthma (OR per 10 microg x m(-3) 1.54, 95% CI 1.00-2.36) and the levels of nitrogen dioxide (NO(2)), which remained statistically significant after adjusting for potential confounders. The relationship between asthma and NO(2) was not significantly modified by sex, hay fever or wheeze. The risk of developing asthma was also significantly related to living close to a major road. The current study suggests that elevated levels of vehicle exhaust outside the home increase the risk of onset and incident asthma among adults.

Occupational skin exposure to water: a population-based study.

BACKGROUND: Occupational exposure to skin irritants, in particular to water, is an important risk factor for hand eczema. OBJECTIVES: To assess occupational skin exposure to water in the general population. METHODS: As part of a public health survey in Stockholm, Sweden, 18,267 gainfully employed individuals aged 18-64 years completed a questionnaire with previously validated questions regarding occupational skin exposure to water. RESULTS: Altogether 16% reported exposure to water for (1/2) h or more a day, and 13% reported exposure to water more than 10 times a day. Furthermore, 7% reported water exposure of more than 2 h and 6% of more than 20 times a day. Women reported more water exposure than men and many female-dominated occupations were seen to comprise water exposure. Women were also more exposed than men within the same jobs. Young adults were more exposed than older. A total of 18% were employed in high-risk occupations for hand eczema. Fifty-nine per cent of individuals employed in high-risk occupations reported water exposure at work, compared with 11% in low-risk occupations. CONCLUSIONS: A total of 20% of the population of working age acknowledged occupational skin exposure to water, which was found to be more common in young adults and women. Using job title as a proxy for water exposure gives an underestimation due to misclassification. In assessing occupational skin exposure to water, both exposure time and frequency should be considered.

Incidence of surgically treated osteoarthritis in the hip and knee in male construction workers.

OBJECTIVE: Occupational workload has been associated with an increased risk of osteoarthritis. The objective was to further examine the association between workload and occurrence of osteoarthritis and in particular to study whether heavy workload has similar importance as a causative factor for osteoarthritis of the hip and knee. METHODS: In a cohort study, the authors investigated the incidence of surgically treated osteoarthritis in the hip and knee among men employed in the Swedish construction industry (n = 204 741). Incident cases were found by linkage with the Swedish hospital discharge register between 1987 and 1998. Incidence rates adjusted for age and BMI were compared between different occupational groups. RESULTS: The incidence rates for osteoarthritis in hip and knee were positively correlated (r = 0.62; p = 0.01). There was a significantly increased risk of surgically treated osteoarthritis in the knee among floor layers, asphalt workers, sheet-metal workers, rock workers, plumbers, brick layers, wood workers and concrete workers. Even if there was a trend towards increased relative risks for osteoarthritis in the hip in floor layers, asphalt workers, wood workers and concrete workers they were not statistically significant. The relative risk for surgically treated osteoarthritis of the knee was 4.7 (95% CI 1.8 to 12.3) among floor layers, indicating an attributable fraction for work factors of 79%. CONCLUSIONS: This study shows that some work-related factors seem to be risk factors for osteoarthritis both in the knee and hip. However, the risk factors seem to be of greater importance for osteoarthritis in the knee compared with the hip. This study indicates that at least 50% of the cases of severe osteoarthritis of the knee can be prevented through decreasing occupational risk factors in some occupational groups.

Asbestos exposure and differences in occurrence of peritoneal mesothelioma between men and women across countries.

OBJECTIVE: In several countries the incidence of peritoneal mesotheliomas among women closely mirrors the pattern among men. The aim was to investigate the role of asbestos exposure in the aetiology of peritoneal mesotheliomas in women and men. METHODS: All cases of peritoneal mesothelioma were selected from the Swedish and Netherlands Cancer Registers for the period 1989-2003. For both countries incidence rates were calculated and stratified by sex. A linear regression analysis was used to analyse the existence of a trend over time. RESULTS: Among men the incidence rate of peritoneal mesothelioma in the Netherlands (0.60 per 100 000 persons) was consistently higher than in Sweden with an average ratio of 1.8 (range 1.4-2.8). In both countries no trend over time was observed. During the 15-year period in the Netherlands the incidence rate among men was about 3.3-fold higher than among women. In Sweden the incidence rate among women was slightly higher than in men up to 1999, and thereafter about threefold higher among men. This sudden shift was statistically significant and seemed mainly caused by changes in classification of peritoneal tumours. CONCLUSION: The absence of a time trend in the incidence rate of peritoneal mesothelioma in the Netherlands and Sweden in the past 15 years may point to a more limited role of occupational exposure to asbestos in the aetiology of peritoneal mesothelioma than for pleural mesothelioma, especially among women. The observed drop around 2000 in annual incidence of peritoneal mesothelioma among Swedish women indicates the presence in the past of a substantial misclassification with other tumours in the peritoneum.

Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers.

BACKGROUND: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). PATIENTS AND METHODS: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). RESULTS: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.

Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions.

It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n=124), lung cancer (n=116) and myeloid leukemia (n=169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P<0.001, mean CVC of 6.60, P=0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C>T (mean prediction error of 22%, P<0.001, mean CVC consistency of 7.40, P<0.037). For leukemia, a 3-loci model including RAD52-2259C>T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P<0.001) and a maximum CVC of 4.40 (P=0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.

Persistence of respiratory symptoms in ex-underground iron ore miners.

AIMS: To assess the persistence of respiratory symptoms in ex-miners after cessation of mining exposure. METHODS: Population-based cross-sectional study using a postal questionnaire comparing prevalence of symptoms between ex-miners who had stopped mining at least 1 year before the study and referents not occupationally exposed to irritants or dust. Age, smoking and a family history of asthma were considered as possible confounders in the analysis. RESULTS: A total of 206 ex-miners and 4,560 referents participated. Ex-miners had on average been working as miners for 13 years and had stopped mining 16 years before the study. Chronic productive cough and physician-diagnosed chronic bronchitis were significantly more common among ex-miners (P < 0.05 and <0.01, respectively). Furthermore, there was a trend that other respiratory symptoms were more common in ex-miners. CONCLUSION: Ex-miners had an increased risk of chronic productive cough and physician-diagnosed chronic bronchitis many years after they had stopped working as a miner.

Vehicle exhaust exposure in an incident case-control study of adult asthma.

The objective of this case-control study was to evaluate whether traffic-related air pollution exposure at home increases the risk of asthma in adults and to compare two commonly used exposure variables and differences between urban and rural living. Incident cases of asthma and matched controls of subjects aged 20-60 yrs were recruited in Luleå, Sweden. In total 203 cases and 203 controls were enrolled in the study. Exposure was estimated by traffic flow and measured levels of outdoor nitrogen dioxide (NO2) in the surrounding environment of each home, respectively. The relationship between measured levels of NO2 and traffic flow was studied using linear regression. The results indicated a nonsignificant tendency between living in a home close to a high traffic flow and an increased risk of asthma. The association between asthma and measured NO2 was weak and not significant, but the skin-prick test result acted as an effect modifier with a borderline significant association among positives. The correlation between traffic flow and outdoor NO2 was low. The results suggest that living close to high traffic flows might increase the asthma incidence in adults, while the tendency for nitrogen dioxide was only seen among atopics. Traffic flow and nitrogen dioxide had a lower than expected correlation.

Airway inflammation in iron ore miners exposed to dust and diesel exhaust.

The aim of the present study was to investigate if underground miners exposed to dust and diesel exhaust in an iron ore mine would show signs of airway inflammation as reflected in induced sputum. In total, 22 miners were studied, once after a holiday of at least 2 weeks and the second time after 3 months of regular work. Control subjects were 21 "white-collar" workers. All subjects completed a questionnaire regarding medical and occupational history, and underwent lung function testing and induced sputum collection. Total and differential cell counts and analyses of the fluid phase of the induced sputum were performed. Sampling of personal exposure to elemental carbon, nitrogen dioxide and inhalable dust was recorded. The average concentrations of inhalable dust, nitrogen dioxide and elemental carbon were 3.2 mg.m-3, 0.28 mg.m-3 and 27 microg.m-3, respectively. Miners had increased numbers of inflammatory cells, mainly alveolar macrophages and neutrophils, and increased concentrations of fibronectin, metalloproteinase-9 and interleukin-10 in induced sputum compared with controls. In conclusion, miners in an underground iron ore mine demonstrated persistent airway inflammation that was as pronounced after a 4-week holiday as after a 3-month period of work underground in the mine.

Fifteen-year follow-up of hand eczema: persistence and consequences.

BACKGROUND: Hand eczema is a skin disease often with a long-lasting and relapsing course. The long-term prognosis in the general population is unknown. OBJECTIVES: The aims were to examine the extent to which hand eczema had persisted and the medicosocial consequences of the disease. METHODS: In a 15-year follow-up of hand eczema, patients diagnosed in a previous population-based study were sent a questionnaire with 20 questions concerning the persistence and course of the disease, and its occupational and medicosocial consequences. RESULTS: Addresses were available for 1115 persons, of whom 868 answered the questionnaire. Sixty-six per cent of the respondents reported periods of hand eczema and 44% reported symptoms during the previous year, with no sex difference. Twelve per cent reported continuous eczema. However, 74% of those reporting symptoms considered that their hand eczema had improved; of these more were women than men (78% vs. 66%, P < 0.01). Twenty people, 3% of those who were gainfully employed in 1983, reported a change to another occupation because of their hand eczema, 15 of these reporting improvement after the job change. A considerable need for medical consultation was reported, as was the influence on psychosocial functions among those who had eczema the previous year, e.g. sleep disturbances (36%) and hampered leisure activities (72%). Job changes related to hand eczema and psychosocial impairment were also reported by individuals who had not sought medical help for their hand eczema. CONCLUSIONS: This study demonstrates a variable and poor long-term prognosis for hand eczema in the general population. One-third sought medical care during follow-up, while the vast majority with ongoing hand eczema experienced negative psychosocial consequences. For about 5%, the hand eczema gave far-reaching consequences including long sick-leave periods, sick pension and changes of occupation.

Obesity increases the risk of incident asthma among adults.

The annual incidence of asthma in adults in northern Sweden has been estimated at 2.3 per thousand population. Risk factors for incident asthma among adults were studied in a case-referent study based on incident cases of asthma during 1995-1999. The healthcare providers reported suspected cases of incident asthma. After clinical examination, 309 (65% female) of 473 reported subjects were included. Inclusion criteria were a history of incident asthma (onset <12 months) and verified bronchial variability. Referents were randomly selected and stratified by age, sex and area of residence. The significant risk factors were hay fever, a family history of asthma, ex-smoking status and elevated body mass index (25.0-29.9 and > or =30). The risk factor pattern was similar for females and males, and increased body mass index was a significant risk factor for both males and females, as well as for allergic and nonallergic subjects. In conclusion, in addition to hay fever, a family history of asthma, allergic sensitisation and ex-smoking status, increased body mass index was a significant risk factor for incident asthma independent of sex and allergic status.

Increased mortality in COPD among construction workers exposed to inorganic dust.

The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.

Risk of fatal industrial accidents and death from other external causes among asphalt workers.

The hypothesis that asphalt workers are at increased risk of mortality from industrial accidents and other external causes was tested. Mortality rates for external and violent causes of death in a cohort of asphalt industry employees from seven European countries and Israel were compared to that of the general population. There was no evidence that mortality from external causes was increased among long term employees in asphalt application and mixing. There was an increased risk for mortality due to external causes among short term workers. However, none of the fatal accidents among short term workers appear to have occurred during employment in the studied asphalt companies. Overall, no evidence was found supporting the hypothesis that asphalt workers are at increased risk of fatal industrial or road accidents. Mortality from other external causes did not increase in this population as a whole, but increased risks among short term workers deserve further attention.