Syncarcinogenesis of natural UV radiation and polycyclic aromatic hydrocarbons in the development of squamous cell carcinomas of the skin?

Squamous cell carcinomas (SCC) of the skin can be induced by occupational exposures to polycyclic aromatic hydrocarbons (PAHs), as in tar and soot, or to UV radiation and can be recognized and compensated as occupational diseases. A possible syncarcinogenic effect of these exposures in the development of SCC in humans is under discussion. For the scientific validation of this question, a systematic literature search was conducted using the databases PubMed, Web of Science, and Scopus. Studies on individuals with SCC of the skin and their precursors as well as occupational, non-occupational, or therapeutic exposure to UV radiation and PAHs were selected. In addition, animal studies with exposure to UV radiation and PAHs were evaluated. After screening the abstracts of 510 identified studies, the full texts of 131 studies were reviewed. None of the epidemiological studies provided robust evidence for a syncarcinogenesis of PAHs and UV radiation in the development of SCC of the skin in humans. Nevertheless, as there are indications for a (super-)additive effect of UV radiation and PAH exposure from animal studies and mechanistic investigations, syncarcinogenesis seems possible. However, quantitative dose-response relationships are lacking which would allow comparison of the onset of an adverse effect between the different exposure levels.

[Occupation-related cancer in urology-Current knowledge including environmental medical aspects]. / Berufsbedingte Krebserkrankungen in der Urologie ­ aktuelle Erkenntnisse unter Einbeziehung umweltmedizinischer Aspekte.

Occupation-related cancers are of considerable importance, which is not yet adequately recognized in the field of urology. The three numerically most significant entities are tumors of the urinary tract caused by carcinogenic aromatic amines or polycyclic aromatic hydrocarbons, renal cell cancer after high exposure to the solvent trichloroethylene, and mesotheliomas of the tunica vaginalis of the testis after exposure to asbestos; however, these can only be recognized as occupation-related if an occupational history regarding the hazard relevant to the organ bearing the tumor is documented from the beginning of employment, e.g. by a questionnaire. This is because the relevant exposures generally date back several decades. With the exception of high exposure to trichloroethylene, the substances mentioned can also environmentally trigger the same tumors. In the context of environmental risk factors, it is of considerable importance that smoking is now considered to be a trigger for some 50% of all bladder cancers in men and women; however, smoking cessation results in a reduction in smoking-related cancer risk of over 30% after only 3-4 years. Work and commuting accidents, which are considered occupational risks, can lead to urological sequelae. For example, increased tumors of the bladder can occur after spinal cord injury lasting longer than 10 years.

[When must the suspicion of an occupational disease or urological sequelae of an occupational accident be reported? : Legal background, medical obligations and course of the procedure]. / Wann sind der Verdacht auf eine Berufskrankheit oder urologische Folgen eines Arbeitsunfalls anzuzeigen? : Rechtlicher Hintergrund, ärztliche Pflichten und Ablauf des Verfahrens.

Physicians are obliged to report the suspected presence of an occupational disease to the German Social Accident Insurance Institutions or to the state authority responsible for occupational health and safety. In the field of urology, tumors of the urinary tract are the most common, followed by the less common renal cell cancer and mesothelioma of the tunica vaginalis testis; however, for such a suspicion to arise at all, sufficient knowledge of urological occupational diseases must be present and the occupational or work history over the entire training and working life since the beginning of employment must be collected. In daily life the notification often fails at this point. In addition to the legal foundation and the principal course of the procedure, this article explains how a relevant comprehensive medical history by means of questionnaires can contribute to the fact that neither too many or all tumor diseases are unreflectedly reported, nor that occupational diseases are overlooked due to the lack of a medical history or detailed knowledge (or fear of this). Urological sequelae of accidents are often not adequately appreciated in the primary process or may take a long time to develop. In this case reporting the aggravation of the consequences of the accident is essential.

The tissue viability imaging system-Suitable method for discovering minimal skin changes in occupational screenings? Results of a cross-sectional field study.

BACKGROUND: For early detection of initial skin changes in occupational screenings, only few objective assessment systems are available. OBJECTIVES: With the aim of assessing an objective measurement method for hand eczema, we trialed the application of the tissue viability imaging (TiVi) system, quantifying erythema non-invasively by polarized light spectroscopy. MATERIALS AND METHODS: In a field study with 625 employees of a semiconductor production company, 411 were exposed to prolonged wearing of occlusive gloves in the clean room. TiVi system and Hand Eczema Score for Occupational Screenings (HEROS), a quantitative skin score for the hands, were used, supplemented by a standardized personal interview. RESULTS: TiVi values of 65 up to 246 for each hand (palm or back), for each participant summed to overall 289 up to 848 (median 389), were measured. Higher TiVi values were noted for men, smokers, and with increasing age. Correlation between TiVi and HEROS was only weak. Several factors like skin pigmentation, thickness of the skin, or tattoos seem to influence TiVi results. CONCLUSIONS: The practical relevance of one-time measurements with the TiVi system in occupational screenings seems to be limited. Specifically, the TiVi system cannot replace dermatological examinations at the workplace. Notwithstanding, the application for other scientific purposes might be useful.

Occupational UV-Exposure is a Major Risk Factor for Basal Cell Carcinoma: Results of the Population-Based Case-Control Study FB-181.

OBJECTIVE: The aim of this study was to investigate the role of occupational and nonoccupational ultraviolet (UV)-exposure concerning the development of basal cell carcinoma (BCC). METHODS: We undertook a population-based multicenter case-control study. Patients with first incident BCC (n = 836) were propensity score matched by age and sex to controls without skin cancer (n = 836). Sociodemographic characteristics, clinical characteristics, and lifetime UV-exposure were assessed by trained investigators. The differential estimation of occupational and nonoccupational UV-exposure dosages was based on validated instruments and established reference values. Associations were assessed using multivariable-adjusted conditional logistic regression models. RESULTS: Individuals with high levels of occupational UV-exposure were at significantly increased BCC-risk compared with individuals with low [odds ratio (OR) 1.84; 95% confidence interval (95% CI) 1.19 to 2.83 and moderate (OR 1.97; 95% CI 1.20 to 3.22) occupational UV-exposure. Nonoccupational UV-exposure was not independently associated with BCC. CONCLUSION: Skin cancer prevention strategies should be expanded to the occupational setting.

The Health Effects of Aluminum Exposure.

BACKGROUND: Aluminum is regularly taken up with the daily diet. It is also used in antiperspirants, as an adjuvant for vaccination, and in desensitization procedures. In this review, we present the scientifically documented harmful effects of aluminum on health and the threshold values associated with them. METHODS: This review is based on publications retrieved by a selective search of the PubMed and SCOPUS databases on the topic of aluminum in connection with neurotoxicity, Alzheimer's disease, and breast cancer, as well as on the authors' personal experience in occupational and environmental medicine. RESULTS: The reference values for the internal aluminum load (<15 µg/L in urine, <5 µg/L in serum) are especially likely to be exceeded in persons with occupational exposure. The biological tolerance value for occupational exposure is 50 µg of aluminum per gram of creatinine in the urine. For aluminum welders and workers in the aluminum industry, declining performance in neuropsychological tests (attention, learning, memory) has been found only with aluminum concentrations exceeding 100 µg/g creatinine in the urine; manifest encephalopathy with dementia was not found. Elevated aluminum content has been found in the brains of persons with Alzheimer's disease. It remains unclear whether this is a cause or an effect of the disease. There is conflicting evidence on carcinogenicity. The contention that the use of aluminum-containing antiperspirants promotes breast cancer is not supported by consistent scientific data. CONCLUSION: The internal aluminum load is measured in terms of the concentration of aluminum in urine and blood. Keeping these concentrations below the tolerance values prevents the development of manifest and subclinical signs of aluminum toxicity. Large-scale epidemiologic studies of the relationship between aluminum-containing antiperspirants and the risk of breast cancer would be desirable.

Protection during production: Problems due to prevention? Nail and skin condition after prolonged wearing of occlusive gloves.

Wearing of occlusive gloves during the whole working shift is considered a risk factor for developing hand eczema, similar to wet work. Moreover, the increased hydration due to glove occlusion may lead to brittle nails. Two hundred and seventy clean room workers, wearing occlusive gloves for prolonged periods, and 135 administrative employees not using gloves were investigated. This included a dermatological examination of the nails and the hands, using the Hand Eczema ScoRe for Occupational Screening (HEROS), measurement of transepidermal water loss (TEWL), and a standardized interview. Of the clean room workers, 39%, mainly women, reported nail problems, mostly brittle nails with onychoschisis. Skin score values showed no significant differences between HEROS values of both groups. TEWL values of exposed subjects were similar to TEWL values of controls 40 min after taking off the occlusive gloves. In a multiple linear regression analysis, male gender and duration of employment in the clean room were associated with a significant increase in TEWL values. The effect of occlusion on TEWL seems to be predominantly transient and not be indicative of a damaged skin barrier. This study confirmed the results of a previous investigation showing no serious adverse effect of wearing of occlusive gloves on skin condition without exposure to additional hazardous substances. However, occlusion leads to softened nails prone to mechanical injury. Therefore, specific prevention instructions are required to pay attention to this side effect of occlusion.

Retrospective evaluation of exposure to natural UV radiation: experiences with the online UV history tool in a field study.

BACKGROUND: Cutaneous squamous cell carcinoma and multiple actinic keratoses can be recognized as occupational diseases if the site affected has been subjected to additional occupational UV exposure of at least 40 %. An online UV history tool that allows for the quantification of occupational and recreational UV doses was now tested in a field study. PATIENTS AND METHODS: Ninety-nine patients with nonmelanoma skin cancer were examined. Patient history with respect to UV exposure was obtained using the online UV history tool. Initial validation was carried out with data from ten additional patients. In the context of a pilot study, the applicability of the tool was assessed using a questionnaire. RESULTS: Overall, patient history revealed a UV exposure between 3,792 and 53,163 SEDs. Patients with squamous cell carcinoma, actinic keratoses, or Bowen's disease (n  =  22) had significantly higher SED values and were significantly older (73 vs. 66 years) than patients with basal cell carcinoma (n  =  77). Occupational UV exposure was reported by 19 patients, two of whom showed an additional occupational UV exposure of more than 40 %, which prompted the filing of a (suspected) occupational disease report. With respect to validation, there was evidence of good inter-investigator reliability. The applicability of the tool was rated as good. CONCLUSIONS: The online UV history tool enables quick retrospective quantification of occupational and recreational UV exposure in case of suspicion of the occupational disease "cutaneous squamous cell carcinoma or multiple actinic keratoses caused by natural UV radiation".

Has dry/cold weather an impact on the skin condition of cleanroom workers?

In previous epidemiological studies irritant skin changes were reported significantly more frequently under dry/cold ambient air conditions. The aim of this study was to assess whether a similar effect might be observed in cleanroom workers, occupationally exposed to strictly controlled ambient conditions. This investigation examined 690 employees of a semiconductor production company in Germany, one half in winter (n = 358) and the other half in spring (n = 332). In both waves, both cleanroom workers, who used occlusive gloves predominantly during the entire shift, and employees in the administration, serving as the control group, were included. Ambient outdoor temperature and relative humidity (RH) were measured and absolute humidity (AH) was calculated. Hands were dermatologically examined with quantitative clinical skin score HEROS, supplemented by transepidermal water loss (TEWL) and stratum corneum hydration measurements. Temperature ranged from -5.41 to 6.51°C in winter (RH 71.04-92.38%; AH 2.85-6.7 g/m3) and from 6.35 to 10.26°C in spring (RH 76.17-82.79%; AH 5.66-7.92 g/m3). Regarding HEROS, TEWL, and corneometry, no marked consistent pattern regarding an enhanced or decreased risk of irritant skin changes was found. Work in a strictly controlled environment with prolonged wearing of occlusive gloves, with clean hands and without exposure to additional hazardous substances, did not seem to negatively affect the skin. In this particular setting, meteorological conditions also did not appear to adversely affect the skin. It is conceivable that wearing of gloves and air conditioning in the plant protect skin of the hands from adverse effects due to dry and cold air encountered when not working.

[Tracing for arsenic exposure--a differentiation of arsenic compounds is essential for the health assessment]. / Der Arsenbelastung auf der Spur.

Arsenic is ubiquitous and harmful to health in occupation and environment. Arsenic exposure is measured through analysis of arsenic compounds in urine. The identification of several arsenic species is necessary to understand the hazardous potential of the arsenic compounds which differ highly in their toxicity. To estimate the extent of an occupational exposure to arsenic, arsenic species were evaluated for the first time by the working group "Setting of Threshold Limit Values in Biological Material" of the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area and Biologische Arbeitsstoffreferenzwerte (BAR) of 0.5 µg / L urine for arsenic (III), 0.5 µg / L urine for arsenic (V), 2 µg / L urine for monomethylarsonic acid (MMA) and 10 µg / L urine for dimethylarsinic acid (DMA) were set. If the reference value for total arsenic is exceeded, a further differentiation of arsenic species now enables to estimate the individual health risks taking into account special influences such as seafood consumption.

Determination of cadmium in biological samples.

Analyses of cadmium concentrations in biological material are performed using inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), but also electrochemical methods, neutron activation analysis (NAA), and X-ray fluorescence spectrometry (XRF). The predominant sample matrices include blood, plasma, serum, and urine, as well as hair, saliva, and tissue of kidney cortex, lung, and liver. While cadmium in blood reveals rather the recent exposure situation, cadmium in urine reflects the body burden and is an indicator for the cumulative long term exposure.After chronic exposure, cadmium accumulates in the human body and causes kidney diseases, especially lesions of proximal tubular cells. A tubular proteinuria causes an increase in urinary excretion of microproteins. Excretions of retinol binding protein (RBP), ß2-microglobulin (ß2-M), and α1-microglobulin are validated biomarkers for analyzing cadmium effects. For this purpose, immunological procedures such as ELISA, and radio- and latex-immunoassays are used.However, proteinuria is not specific to cadmium, but can also occur after exposure to other nephrotoxic agents or due to various kidney diseases. In summary, cadmium in urine and blood are the most specific biomarkers of cadmium exposure. A combination of parameters of exposure (cadmium in blood, cadmium in urine) and parameters of effect (e.g., ß2-M, RBP) is required to reveal cadmium-induced nephrological effects.

N-Acetyltransferase 2 and glutathione s-transferase M1 in colon and rectal cancer cases from an industrialized area.

Apart from genetics, nutrition, and environment, occupational factors also play an important role in colon and rectal cancer development. The aim of this study was to examine these cancer types in an area of former coal, iron, and steel industries, which was found to display an increased incidence of colon cancer mortality. N-Acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) genotypes were investigated in 108 colon cancer cases, 80 rectum cancer cases, and 188 controls (suffering from nonmalignant diseases). Further, in a pilot study, 28 colorectal cancer patients were NAT2 phenotyped by the caffeine test. Possible occupational and nonoccupational risk factors were investigated by a personal interview. The frequency of rapid NAT2 genotype was 35% in colon cancer cases, 47% in rectal cancer cases, and 42% in controls (GSTM1 0/0 genotype: 53, 46, and 47%, respectively). In the 29 patients with cancer in the ascending colon, 10% were of the rapid NAT2 genotype. In the pilot study the frequency of the rapid NAT2 phenotype was 49%. The only major professional group with an elevated risk was painters (colon cancer OR 2.48, 95% CI 0.4-15.23; rectal cancer OR 5.65, 95% CI 1.06-30.21). In contrast to early studies, in the present study the slow NAT2 status is overrepresented. As colorectal cancer is associated with nutrition and physical activity, present findings may be due to excessive physical heavy work and the resulting nutrition in this area.

Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk.

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

On the lookout for precursor lesions: where does dry skin end and slight hand eczema begin?

BACKGROUND: The prognosis of occupational hand eczema is strongly associated with its duration, severity, and the onset of treatment. OBJECTIVES: The study was aimed at characterizing skin eruptions that might be potential precursors of occupational hand eczema, their pattern, and typical sites in a population at moderate risk of hand eczema. PATIENTS/MATERIALS/METHODS: Eight hundred German male metal workers took part in a structured interview focused on their medical history combined with a dermatological examination of their hands, by use of the quantitative Hand Eczema Score for Occupational Screenings, with follow-up 1 year later. RESULTS: The most frequent lesions were erythema (91.8%), lichenification (98.8%), crusting (70%), and scaling (35%); all other lesions were relatively rare (15%). The distribution of lesions remained stable between baseline and follow-up. The areas most affected were knuckles, palms, and finger shafts (excluding tips). Interdigital regions were uncommonly affected in this sample. CONCLUSIONS: Erythema, lichenification, and crusting, indicating constant skin 'strain', can be regarded as precursor lesions for slight hand eczema, and should be monitored quantitatively. As other occupations, for example hairdressing, have different predilection sites, it can be concluded that the pattern of occupational hand eczema is strongly influenced by the distinct strain profile of an occupation.

Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk.

Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n = 948/1,258), Hungary (n = 262/65), Venezuela (n = 112/190) and Pakistan (n = 103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR = 1.21; 95% Cl = 1.04-1.40; P = 0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR = 1.23; 95% Cl = 1.05-1.44; P = 0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR = 1.18; 95% Cl = 1.12-1.25; P < 0.0001). However, the odds ratio is relatively small.