Incidence of malignant mesothelioma in Germany 2009-2013.

PURPOSE: The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce. METHODS: We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient's residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany. RESULTS: In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013-90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men. CONCLUSION: Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.

Oxidatively damaged guanosine in white blood cells and in urine of welders: associations with exposure to welding fumes and body iron stores.

The International Agency for Research on Cancer considers the carcinogenicity of welding fume of priority for re-evaluation. Genotoxic effects in experimental animals are still inconclusive. Here, we investigated the association of personal exposure to metals in respirable welding fumes during a working shift with oxidatively damaged guanosine in DNA of white blood cells (WBC) and in postshift urine samples from 238 welders. Medians of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were 2.35/10(6) dGuo in DNA of WBC and 4.33 µg/g creatinine in urine. The median of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 7.03 µg/g creatinine in urine. The extent of both urinary parameters was higher in welders applying techniques with high particle emission rates to stainless steel than in tungsten inert gas welders (8-oxodGuo: 9.96 vs. 4.49 µg/L, 8-oxoGuo: 15.7 vs. 7.7 µg/L), but this apparent difference diminished after creatinine adjustment. We applied random intercept models to estimate the influence of airborne and systemic exposure to metals on oxidatively damaged guanosine in WBC and urine together with covariates. We observed a highly significant nonlinear association of urinary 8-oxoGuo with serum ferritin (P < 0.0001) and higher 8-oxoGuo concentrations for respirable iron >1,000 µg/m(3) compared to ≤57 µg/m(3). Similar effects were found for manganese. Airborne chromium but not nickel was associated with all oxidatively modified guanosine measures, whereas urinary chromium as well as nickel showed associations with urinary modified guanosines. In summary, oxidatively damaged urinary guanosine was associated with airborne and systemic exposure to metals in welders and showed a strong relation to body iron stores.

Reduction in welding fume and metal exposure of stainless steel welders: an example from the WELDOX study.

PURPOSE: In a plant where flux-cored arc welding was applied to stainless steel, we investigated changes in airborne and internal metal exposure following improvements of exhaust ventilation and respiratory protection. METHODS: Twelve welders were examined at a time in 2008 and in 2011 after improving health protection. Seven welders were enrolled in both surveys. Exposure measurement was performed by personal sampling of respirable welding fume inside the welding helmets during one work shift. Urine and blood samples were taken after the shift. Chromium (Cr), nickel (Ni), and manganese (Mn) were determined in air and biological samples. RESULTS: The geometric mean of respirable particles could be reduced from 4.1 mg/m(3) in 2008-0.5 mg/m(3) in 2011. Exposure to airborne metal compounds was also strongly reduced (Mn: 399 vs. 6.8 µg/m(3); Cr: 187 vs. 6.3 µg/m(3); Ni: 76 vs. 2.8 µg/m(3)), with the most striking reduction inside helmets with purified air supply. Area sampling revealed several concentrations above established or proposed exposure limits. Urinary metal concentrations were also reduced, but to a lesser extent (Cr: 14.8 vs. 4.5 µg/L; Ni: 7.9 vs. 3.1 µg/L). Although biologically regulated, the mean Mn concentration in blood declined from 12.8 to 8.9 µg/L. CONCLUSION: This intervention study demonstrated a distinct reduction in the exposure of welders using improved exhaust ventilation and welding helmets with purified air supply in the daily routine. Data from area sampling and biomonitoring indicated that the area background level may add considerably to the internal exposure.

Exposure to inhalable, respirable, and ultrafine particles in welding fume.

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements

Assessment of micronuclei in lymphocytes from workers exposed to vapours and aerosols of bitumen.

We investigated the micronucleus frequencies in peripheral blood lymphocytes of 225 mastic asphalt workers (age 17-62 years) and 69 non-bitumen-exposed road construction workers (age 18-64 years) in Germany before and after the working shift. Median shift exposure to vapours and aerosols of bitumen of exposed workers was 3.0 mg/m³. Micronuclei (MN) were determined with a standard method using cytochalasin B. Median MN frequency was 6.0 (interquartile range (IQR) 4.0-8.5) MN/1,000 binucleated lymphocytes (MN/1,000 BNC) in exposed workers and 6.0 (IQR 4.0-8.3) MN/1,000 BNC in non-exposed workers before shift. After shift, we observed 6.5 (IQR 4.4-9.3) MN/1,000 BNC in exposed workers and 6.5 (IQR 4.0-9.0) MN/1,000 BNC in non-exposed workers. Regression models were applied with the log-transformed MN frequency as the dependent variable in order to estimate the effects of exposure to vapours and aerosols of bitumen and of potential confounders. Age was the strongest predictor of MN formation in both exposed workers and referents. Our data suggest that MN formation was not associated with concentration of vapours and aerosols of bitumen during shift at the individual level. Although similar MN frequencies were observed in both groups, the modelling of factors potentially influencing MN frequency revealed a weak group difference in the post-shift model. We conclude that this small difference cannot be judged to be a relevant mutagenic effect of exposure to vapours and aerosols of bitumen, also with regard to the lack of adjustment for multiple testing and the lack of a group effect in the original data.

Modulation of urinary polycyclic aromatic hydrocarbon metabolites by enzyme polymorphisms in workers of the German Human Bitumen Study.

Data concerning the influence of sequence variants of metabolizing enzymes on the effect modulation of current exposure to vapors and aerosols of bitumen in humans are limited. To assess the influence of 18 single-nucleotide polymorphisms (SNP) in genes coding for enzymes involved in polycyclic aromatic hydrocarbon (PAH) and amine metabolism regarding their impact on urinary markers 1-hydroxpyrene (1-OHP) and the sum of 1-, 2+9-, 3-, 4-hydroxyphenanthrene (OHPHE). Based on personal ambient monitoring data for bitumen emissions, 218 German workers exposed to vapors and aerosols of bitumen during a shift and 96 German roadside construction workers without exposure to bitumen but with similar working tasks were studied. SNP determination based on DNA aliquots isolated from blood samples by real-time PCR or direct sequencing. The impact of sequence variants on the urinary levels of 1-OHP and sum of OHPHE was estimated with mixed linear models, adjusted for age, creatinine, exposure, smoking, SNP, and time of measurement. In the mixed linear model, an increasing metabolite level of OHPHE was only slightly modulated by the CC variant of the cytochrome P450 SNP CYP1A1 3801T>C (rs4646903; P = 0.051). In contrast, GSTM1 carriers showed a significant (P= 0.046) and double-mutated variants of three NAT2-specific SNP (NAT2*341CC, P = 0.06; NAT2*481TT, P = 0.06; NAT2*803GG, P = 0.042) displayed a decreasing influence on OHPHE levels. None of the SNP studied showed a significant effect on 1-OHP. The modulating SNP effects on OHPHE in the adjusted model were less pronounced when compared with the effects observed in a recent study with 170 workers occupationally exposed to PAH in German industries. This may be due to the much lower PAH exposure in the Human Bitumen Study.

Bitumen workers handling mastic versus rolled asphalt in a tunnel: assessment of exposure and biomarkers of irritation and genotoxicity.

Emission levels of vapours and aerosols of bitumen are different when processing rolled asphalt compared to mastic asphalt, with working temperatures up to 180 and 250°C, respectively. During the Human Bitumen Study, we examined six workers handling rolled asphalt and mastic asphalt in two consecutive weeks at the same construction site in a tunnel. In addition to the determination of exposure to bitumen and polycyclic aromatic hydrocarbons (PAH) during shift, we examined urinary PAH metabolites, irritative and genotoxic effects before and after shift. Median personal shift concentration of vapours and aerosols of bitumen was 1.8 (range 0.9-2.4) mg/m(3) during the application of rolled asphalt and 7.9 (range 4.9-11.9) mg/m(3) when mastic asphalt was applied. Area measurement of vapours and aerosols of bitumen revealed higher concentrations than the personal measurements for mastic asphalt (mastic asphalt: 34.9 mg/m(3); rolled asphalt: 1.8 mg/m(3)). Processing mastic asphalt was associated also with higher PAH concentrations. Urinary 1-hydroxypyrene and the sum of 1-, 2+ 9-, 3- and 4-hydroxyphenanthrene increased slightly during shift without clear difference between mastic and rolled asphalt application. However, the post-shift urinary PAH-metabolite concentrations did not reflect the different PAH exposure during mastic and rolled asphalt application. Individual workers could be identified by their spirometry results indicating that these data reflect more chronic than acute effects. In most cases, an increase of 8-oxodGuo adducts was observed during shift that was independent of the asphalt application. 8-oxodGuo and (+)-anti-BPDE-DNA adducts were higher than in exposed workers of the Human Bitumen Study independent of the asphalt application. The DNA-strand breaks were considerably higher pre-shift and decreased during shift. In this study, mastic asphalt application led to significantly higher exposure to vapours and aerosols of bitumen, as well as to airborne PAH, compared to rolled asphalt application. Nevertheless, no differences in the excretion of urinary PAH metabolites, lung function impairment and genotoxic markers were detected. However, higher levels of genotoxicity markers on both examination days compared with the results of the Human Bitumen Study may indicate a possible influence of the specific tunnel setting.

DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect.

To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.

Levels and determinants of exposure to vapours and aerosols of bitumen.

Bitumen (referred to as asphalt in the United States) is a widely used construction material, and emissions from hot bitumen applications have been a long-standing health concern. One objective of the Human Bitumen Study was to identify potential determinants of the exposure to bitumen. The study population analysed comprised 259 male mastic asphalt workers recruited between 2003 and 2008. Personal air sampling in the workers' breathing zone was carried out during the shift to measure exposure to vapours and aerosols of bitumen. The majority of workers were engaged in building construction, where exposure levels were lower than in tunnels but higher than at road construction sites. At building construction sites, exposure levels were influenced by the room size, the processing temperature of the mastic asphalt and the job task. The results show that protective measures should include a reduction in the processing temperature.

Air sampling and determination of vapours and aerosols of bitumen and polycyclic aromatic hydrocarbons in the Human Bitumen Study.

The chemical complexity of emissions from bitumen applications is a challenge in the assessment of exposure. Personal sampling of vapours and aerosols of bitumen was organized in 320 bitumen-exposed workers and 69 non-exposed construction workers during 2001-2008. Area sampling was conducted at 44 construction sites. Area and personal sampling of vapours and aerosols of bitumen showed similar concentrations between 5 and 10 mg/m(3), while area sampling yielded higher concentrations above the former occupational exposure limit (OEL) of 10 mg/m(3). The median concentration of personal bitumen exposure was 3.46 mg/m(3) (inter-quartile range 1.80-5.90 mg/m(3)). Only few workers were exposed above the former OEL. The specificity of the method measuring C-H stretch vibration is limited. This accounts for a median background level of 0.20 mg/m³ in non-exposed workers which is likely due to ubiquitous aliphatic hydrocarbons. Further, area measurements of polycyclic aromatic hydrocarbons (PAHs) were taken at 25 construction sites. U.S. EPA PAHs were determined with GC/MS, with the result of a median concentration of 2.47 µg/m(3) at 15 mastic asphalt worksites associated with vapours and aerosols of bitumen, with a Spearman correlation coefficient of 0.45 (95% CI -0.13 to 0.78). PAH exposure at mastic-asphalt works was higher than at reference worksites (median 0.21 µg/m(3)), but about one order of magnitude lower compared to coke-oven works. For a comparison of concentrations of vapours and aerosols of bitumen and PAHs in asphalt works, differences in sampling and analytical methods must to be taken into account.

Association between genetic polymorphisms in styrene-metabolizing enzymes and biomarkers in styrene-exposed workers.

Single-nucleotide polymorphisms (SNP) in genes of styrene-metabolizing enzymes could modulate biomarker concentrations in blood or urine after exposure to styrene. Ten SNP were analyzed to study their influence on styrene-specific biomarkers in 89 workers of a fiber-reinforced plastic boat building factory. The internal styrene body burden was analyzed in post-shift blood and urine samples. External styrene exposure was measured by passive samplers. Spearman rank correlations between styrene exposure and biomarkers were calculated and distributions of biomarkers were checked for lognormality. Mixed linear models were applied to analyze the influence of genotypes and styrene exposure, on styrene in blood (Monday and Thursday post-shift) and on phenyglyoxylic acid (PGA; adjusted for day of measurement, Monday to Thursday) due to a lognormal distribution, smoking (current, not current), and use of respirators. Stratified analyzes for workers without and with different types of respirators were also performed. The models of both the subgroups revealed a significant influence dependent on the respirator type that workers used for inhalation protection. An influence of the external styrene concentration on the urinary PGA concentration was not observed. After implementation of the SNP into the model significant lower adjusted means of urinary PGA concentrations were found for GSTP1 105IleVal and CYP2E1 -71TT. For styrene levels in blood no significant effect was observed. A significant influence on styrene levels in blood was correlated with external styrene concentration only in workers without use of respirators. The effects of two SNP on urinary PGA decrease indicated a limited modulating SNP effect. The most effective prevention for styrene exposure was obtained with the wearing of respirators.

Exposure to hexavalent chromium in welders: Results of the WELDOX II field study.

Objectives: Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure. Methods: Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (rs) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration. Results: Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50 µg m-3, and 8 out of 50 (16%) welders exceeded 1 µg m-3. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87). Conclusions: The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m-3. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

Cancer mortality in Itapúa--A rural province of Paraguay 2003-2012.

BACKGROUND: Itapúa is a rural department in Paraguay with a population of about 500,000 and a high degree of agro-mechanization for the production of soybean and other crops. So far, only basic health care is provided. Here we analyzed the cancer mortality in this region as a first step towards epidemiological data for cancer prevention. METHODS: We calculated the age-adjusted mortality rates according to world standard (AMRWs) for the major cancer sites in both males and females between 2003 and 2012, and estimated the differences between the capital and more central districts of Itapúa vs. remote districts. RESULTS: There were about 2000 cancer deaths in the decade studied, with AMRWs for all malignancies of 90.9/100,000 in males from central vs. 49.1/100,000 in remote districts and 69.0/100,000 vs. 45.0/100,000 in women. Cancer was mentioned in 12.4% of all death certificates and outweighed mortality from certain infectious and parasitic diseases (3.6%). Cause of death was ill-defined in 19.6% of all death certificates, especially in remote regions and among the elderly. The part of cancer located in the uterus (47.8%) or cell type of neoplasm of the lymphatic or hematopoietic system (73.1%) were often not specified. The uterus (mainly the cervix) (C53-C55) was the leading cancer site in women with AMRWs of 17.2/100,000 in central and 14.0/100,000 in remote districts, followed by the breast. Lung and prostate were the leading cancer sites among men. The lung cancer mortality rate was 19.3/100,000 in the central region but 9.5/100,000 in remote districts. Although children comprised 36% of the population, only 24 death certificates listed cancer as cause of death in this decade. CONCLUSIONS: Analysis of cancer mortality in this rural region of Paraguay, which lacks resources for diagnostics and care, revealed an already large number of cases, with higher rates in the central region than in remote districts. Lung and uterus (primarily the cervix) are common cancer sites and indicate the potential for prevention. However, the quality of the vital statistics needs to be improved. The true cancer burden is most likely underestimated, especially in remote regions and children.

Polymorphisms in circadian genes, night work and breast cancer: results from the GENICA study.

OBJECTIVES: The role of genetic variants and environmental factors in breast cancer etiology has been intensively studied in the last decades. Gene-environment interactions are now increasingly being investigated to gain more insights into the development of breast cancer, specific subtypes, and therapeutics. Recently, night shift work that involves circadian disruption has gained rising interest as a potential non-genetic breast cancer risk factor. Here, we analyzed genetic polymorphisms in genes of cellular clocks, melatonin biosynthesis and signaling and their association with breast cancer as well as gene-gene and gene-night work interactions in a German case-control study on breast cancer. METHODS: GENICA is a population-based case-control study on breast cancer conducted in the Greater Region of Bonn. Associations between seven polymorphisms in circadian genes (CLOCK, NPAS2, ARTNL, PER2 and CRY2), genes of melatonin biosynthesis and signaling (AANAT and MTNR1B) and breast cancer were analyzed with conditional logistic regression models, adjusted for potential confounders for 1022 cases and 1014 controls. Detailed shift-work information was documented for 857 breast cancer cases and 892 controls. Gene-gene and gene-shiftwork interactions were analyzed using model-based multifactor dimensionality reduction (mbMDR). RESULTS: For combined heterozygotes and rare homozygotes a slightly elevated breast cancer risk was found for rs8150 in gene AANAT (OR 1.17; 95% CI 1.01-1.36), and a reduced risk for rs3816358 in gene ARNTL (OR 0.82; 95% CI 0.69-0.97) in the complete study population. In the subgroup of shift workers, rare homozygotes for rs10462028 in the CLOCK gene had an elevated risk of breast cancer (OR for AA vs. GG: 3.53; 95% CI 1.09-11.42). Shift work and CLOCK gene interactions were observed in the two-way interaction analysis. In addition, gene-shiftwork interactions were detected for MTNR1B with NPAS2 and ARNTL. CONCLUSIONS: In conclusion, the results of our population-based case-control study support a putative role of the CLOCK gene in the development of breast cancer in shift workers. In addition, higher order interaction analyses suggest a potential relevance of MTNR1B with the key transcriptional factor NPAS2 with ARNTL. Hence, in the context of circadian disruption, multivariable models should be preferred that consider a wide range of polymorphisms, e.g. that may influence chronotype or light sensitivity. The investigation of these interactions in larger studies is needed.

Levels and predictors of airborne and internal exposure to chromium and nickel among welders--results of the WELDOX study.

The objective of this analysis was to investigate levels and determinants of exposure to airborne and urinary chromium (Cr, CrU) and nickel (Ni, NiU) among 241 welders. Respirable and inhalable welding fume was collected during a shift, and the metal content was determined using inductively coupled plasma mass spectrometry. In post-shift urine, CrU and NiU were measured by means of graphite furnace atom absorption spectrometry, with resulting concentrations varying across a wide range. Due to a large fraction below the limits of quantitation we applied multiple imputations to the log-transformed exposure variables for the analysis of the data. Respirable Cr and Ni were about half of the concentrations of inhalable Cr and Ni, respectively. CrU and NiU were determined with medians of 1.2 µg/L (interquartile range <1.00; 3.61) and 2.9 µg/L (interquartile range <1.50; 5.97). Furthermore, Cr and Ni correlated in respirable welding fume (r=0.79, 95% CI 0.74-0.85) and urine (r=0.55, 95% CI 0.44-0.65). Regression models identified exposure-modulating variables in form of multiplicative factors and revealed slightly better model fits for Cr (R(2) respirable Cr 48%, CrU 55%) than for Ni (R(2) respirable Ni 42%, NiU 38%). The air concentrations were mainly predicted by the metal content in electrodes or base material in addition to the welding technique. Respirable Cr and Ni were good predictors for CrU and NiU, respectively. Exposure was higher when welding was performed in confined spaces or with inefficient ventilation, and lower in urine when respirators were used. In conclusion, statistical modelling allowed the evaluation of determinants of internal and external exposure to Cr and Ni in welders. Welding parameters were stronger predictors than workplace conditions. Airborne exposure was lowest inside respirators with supply of purified air.

Night work and breast cancer estrogen receptor status--results from the German GENICA study.

OBJECTIVES: The potential mechanisms that link night-shift work with breast cancer have been extensively discussed. Exposure to light at night (LAN) depletes melatonin that has oncostatic and anti-estrogenic properties and may lead to a modified expression of estrogen receptor (ER) α. Here, we explored the association between shift work and breast cancer in subgroups of patients with ER-positive and -negative tumors. METHODS: GENICA (Gene-ENvironment Interaction and breast CAncer) is a population-based case-control study on breast cancer with detailed information on shift work from 857 breast cancer cases and 892 controls. ER status was assessed by immunohistochemical staining. Associations between night-shift work and ER-positive and -negative breast cancer were analyzed with conditional logistic regression models, adjusted for potential confounders. RESULTS: ER status was assessed for 827 cases and was positive in 653 and negative in 174 breast tumors. Overall, 49 cases and 54 controls were "ever employed" in shift work including night shifts for ≥ 1 year. In total, "ever shift work" and "ever night work" were not associated with an elevated risk of ER-positive or -negative breast tumors. Night work for ≥ 20 years was associated with a significantly elevated risk of ER-negative breast cancer [odds ratio (OR) 4.73, 95% confidence interval (95% CI) 1.22-18.36]. CONCLUSIONS: Our case-control study suggests that long-term night-shift work is associated with an increased risk of ER-negative breast cancers. Further studies on histological subtypes and the analysis of other potentially relevant factors are crucial for discovering putative mechanisms.

Levels and predictors of airborne and internal exposure to manganese and iron among welders.

We investigated airborne and internal exposure to manganese (Mn) and iron (Fe) among welders. Personal sampling of welding fumes was carried out in 241 welders during a shift. Metals were determined by inductively coupled plasma mass spectrometry. Mn in blood (MnB) was analyzed by graphite furnace atom absorption spectrometry. Determinants of exposure levels were estimated with multiple regression models. Respirable Mn was measured with a median of 62 (inter-quartile range (IQR) 8.4-320) µg/m(3) and correlated with Fe (r=0.92, 95% CI 0.90-0.94). Inhalable Mn was measured with similar concentrations (IQR 10-340 µg/m(3)). About 70% of the variance of Mn and Fe could be explained, mainly by the welding process. Ventilation decreased exposure to Fe and Mn significantly. Median concentrations of MnB and serum ferritin (SF) were 10.30 µg/l (IQR 8.33-13.15 µg/l) and 131 µg/l (IQR 76-240 µg/l), respectively. Few welders were presented with low iron stores, and MnB and SF were not correlated (r=0.07, 95% CI -0.05 to 0.20). Regression models revealed a significant association of the parent metal with MnB and SF, but a low fraction of variance was explained by exposure-related factors. Mn is mainly respirable in welding fumes. Airborne Mn and Fe influenced MnB and SF, respectively, in welders. This indicates an effect on the biological regulation of both metals. Mn and Fe were strongly correlated, whereas MnB and SF were not, likely due to higher iron stores among welders.

Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.

The objective of this analysis was the estimation of the cancer risks of asbestos and asbestosis in a surveillance cohort of high-exposed German workers. A group of 576 asbestos workers was selected for high-resolution computer tomography of the chest in 1993-1997. A mortality follow-up was conducted through 2007. Standardised mortality ratios (SMRs) were calculated and Poisson regression was performed to assess mesothelioma risks. A high risk was observed for pleural mesothelioma (SMR 28.10, 95% CI 15.73-46.36) that decreased after cessation of exposure (RR 0.1; 95% CI 0.0-0.6 for > or =30 vs. <30 years after last exposure). Asbestosis was a significant risk factor for mesothelioma (RR 6.0, 95% CI 2.4-14.7). Mesothelioma mortality was still in excess in former asbestos workers although decreasing after cessation of exposure. Fibrosis was associated with subsequent malignancy.

Night work and breast cancer - results from the German GENICA study.

OBJECTIVES: Some epidemiological and animal data indicate that night work might increase the risk for breast cancer. We have investigated the risk in a German population-based case-control study known as GENICA (gene environment interaction and breast cancer). METHODS: The GENICA study involved interviews to assess shift work information in 857 breast cancer cases and 892 controls. We estimated risks of employment status and night shift characteristics using conditional logistic regression models, adjusting for potential confounders. Resampling and bootstrapping were applied to adjust the risk estimates for a potential selection bias. RESULTS: Among 1749 women, 56 cases and 57 controls worked in night shifts for > or =1 year, usually in the healthcare sector (63.0% of controls). Female night workers were more frequently nulliparous and low-educated than day workers (28.6% versus 17.8% and 12.3% versus 9.2%, respectively). Fewer women in night work had ever used post-menopausal hormone therapy (35.7% versus 51.9%). An elevated breast cancer risk was not associated with having ever done shift or night work when compared to women employed in day work only [odds ratio (OR) 0.96, 95% confidence interval (95% CI) 0.67-1.38 and OR 0.91, 95% CI 0.55-1.49, respectively). Women who reported >807 night shifts, the third quartile of the distribution among controls, experienced a breast cancer risk of 1.73 (95% CI 0.71-4.22). Night work for > or =20 years was associated with an OR of 2.48 (95% CI 0.62-9.99) based on 12 cases and 5 controls. CONCLUSIONS: Long-term night work was associated with a modestly, but not significantly, increased breast cancer risk, while having ever done night work was not. The precision of the results was limited by a low prevalence of night work in this study population.

Development of a 1-concentration-4-step dosimeter protocol for methacholine testing.

Methacholine testing is an important diagnostic tool for asthma. Newly available dosimeter and software technology allows for simplification of the test. This study aimed to evaluate a single-concentration dosimeter protocol for methacholine testing by comparison with a multi-concentration dosimeter protocol similar to that recommended by the American Thoracic Society (ATS) (standard protocol). Fifty young subjects with high pretest probability for bronchial hyperresponsiveness underwent two challenges in randomized order within one week. The novel protocol used a Medic-Aid Sidestream nebulizer and a fixed methacholine concentration of 16mg/mL. Number and duration of nebulizations were matched to the last four doses of the standard protocol, and results were expressed cumulatively. The rank correlation between log slopes (n=50) was 0.86; that between log provocative doses (n=18), which differed at low values, was 0.58. When requiring a 20% fall in FEV(1) at any methacholine dose, 18 subjects were hyperresponsive and 28 normoresponsive in both tests (46/50 concordant). One subject was positive only with the standard, and 3 only with the novel protocol (Cohen's kappa 83%). The novel protocol for methacholine testing yielded qualitative results similar to those of the ATS multi-concentration protocol, although there were quantitative differences at low doses. However, its design and handling may offer advantages for clinical practice.