Bladder cancer course, four genetic high-risk variants, and histopathological findings.

Urinary bladder cancer, a smoking and occupation related disease, was subject of several genome-wide association studies (GWAS). However, studies on the course of the disease based on GWAS findings differentiating between muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) are rare. Thus we investigated 4 single nucleotide polymorphisms (SNPs) detected in GWAS, related to the genes coding for TACC3 (transforming, acidic coiled-coil containing protein 3), for FGFR3 (fibroblast growth factor receptor 3), for PSCA (prostate stem cell antigen) and the genes coding for CBX6 (chromobox homolog 6) and APOBEC3A (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A).

A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers.

Sensory irritation is an acute adverse effect caused by chemicals that stimulate chemoreceptors of the upper respiratory tract or the mucous membranes of the outer eye. The avoidance of this end point is of uttermost importance in regulatory toxicology. In this study, repeated exposures to ethyl acrylate were analyzed to investigate possible carryover effects from day to day for different markers of sensory irritation.

Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit.

-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of , so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel.

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer.

Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations.

Algorithm for the Automated Evaluation of NAT2 Genotypes.

N-Acetyltransferase 2 (NAT2) genotyping by PCR and RFLP-based methods provides information on seven single nucleotide polymorphisms (SNPs) without deriving the chromosomal phase (haplotype). So genotyping results must be processed to get all possible NAT2 haplotype (or allele) combinations. Here we describe the procedure for genotyping and present a program based on Microsoft Access which automatically generates all possible haplotype pairs for a given unphased NAT2 genotype.

Micro-brushing-based technique to gain fresh urothelial cells for gene expression analysis.

The gold standard of saving fresh tissue in liquid nitrogen has some serious disadvantages in that this process is not available in daily medical routine practices even in many tumor centers. Our approach of a new minimally invasive technique is obtaining urothelial cells via micro-brushing the urinary bladder on the occasion of urological routine methods such as transurethral resection (TUR). Urothelial cells were obtained from 25 patients via two different micro-brushes from tumor tissue and from macroscopically healthy tissue during TUR.

N-acetyltransferase 1*10 genotype in bladder cancer patients.

In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT1*10 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk.

Polymorphisms of xenobiotic metabolizing enzymes in bladder cancer patients of the Semmelweis University Budapest, Hungary.

Polymorphic xenobiotic metabolizing enzymes such as N-acetyltransferase 2 (NAT2) or glutathione S-transferase M1 (GSTM1) are known to modulate bladder cancer risk. As no apparent data were available from Hungary, a former member of the eastern European economic organization, a study was performed in Budapest. In total, 182 bladder cancer cases and 78 cancer-free controls were investigated by questionnaire.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped.

Occupational bladder cancer: Polymorphisms of xenobiotic metabolizing enzymes, exposures, and prognosis.

Approximately 7% of all bladder cancer cases in males are associated with occupation. The question arises whether the use of genome-wide association studies was able to identify bladder cancer risk factors that may modulate occupational bladder cancer risk and prognosis. One hundred and forty-three bladder cancer cases with suspected occupational bladder cancer and 337 controls were genotyped for the following polymorphisms: N-acetyltransferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), UDP-glucuronyltransferase 1A rs11892031 (UGT1A), rs9642880 (close to c-MYC), and rs710521 (close to TP63).

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma.

Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration.

Does seasonal allergic rhinitis increase sensitivity to ammonia exposure?

Allergic inflammation in the upper airways represents a wide-spread health issue: Little is known about whether it increases sensitivity to airborne chemicals thereby challenging established exposure limits that neglect such differences in susceptibility. To investigate the role of pre-existing allergic inflammation, 19 subjects with seasonal allergic rhinitis (SAR) and 18 control subjects with low risk of sensitization were exposed for 4h to ammonia in two concentrations (cross-over design): 2.5ppm (odor threshold) and 0-40ppm (occupational exposure limit: 20ppm TWA).

Prediction of human sensory irritation due to ethyl acrylate: the appropriateness of time-weighted average concentration × time models for varying concentrations.

Human data about the potency of ethyl acrylate to evoke sensory irritation is currently not available. Therefore, we conducted an experimental exposure study and the magnitude of chemosensory effects in healthy human volunteers was mathematically modeled by combining the factors current concentration (c) and duration/time (t). In a repeated-measures design, 19 subjects were exposed for 4 h to constant and varying concentrations (including peaks of 5 and 10 ppm) of ethyl acrylate with either a 2.

Biomonitoring of Mycotoxins in Urine: Pilot Study in Mill Workers.

Contamination of grains with mycotoxins results in a dietary background exposure of the general population. In occupational settings such as during processing of raw materials as in milling, an additional mycotoxin exposure by inhalation is possible. Biomonitoring is an integrative approach to assess human exposure from various sources and by all routes.

Occupational risk factors for relapse-free survival in bladder cancer patients.

The influence of occupational risk factors on bladder cancer development is well investigated. However, studies on the influence on bladder cancer prognosis are rare. Therefore, it was of interest to investigate the time to first relapse in the follow-ups of three case-control series from Dortmund, Neuss, and Lutherstadt Wittenberg, Germany.

Interindividual differences in chemosensory perception: Toward a better understanding of perceptual ratings during chemical exposures.

Perceptions that arise from stimulation of olfactory and trigeminal receptors in the nasal cavity guide the evaluation of chemical environment in humans. Strong interindividual differences in these assessments may be attributed to nonsensory factors such as gender, anxiety, and chemical sensitivity. Knowledge regarding the influence of these factors originates mainly from basic odor research using short-term exposure scenarios.

Determination of aflatoxin M in urine samples indicates frequent dietary exposure to aflatoxin B in the Bangladeshi population.

Aflatoxin B (AFB), a hepatocarcinogen and highly toxic mycotoxin, is a contaminant of food commodities, especially in hot and humid climates that favour the growth of aflatoxin-producing fungi. As data on AFB contamination of food and feed in Bangladesh are scarce, we conducted an initial screening by ELISA on the occurrence of the metabolite and biomarker aflatoxin M (AFM) in urines from Bangladesh which indicated frequent exposure. This finding led us to conduct a follow-up study where we applied a more sensitive method (IAC clean-up and HPLC-FD analysis) to determine AFM concentrations in a larger set of urine samples.

Assessment of deoxynivalenol exposure among Bangladeshi and German adults by a biomarker-based approach.

Deoxynivalenol (DON) is a frequent mycotoxin contaminant in cereal crops worldwide and can cause adverse health effects in exposed animals and humans. Since DON contamination in Bangladeshi food is unexplored, we conducted a biomonitoring study to assess DON exposure in the Bangladeshi population and compare it with that of German adults. In total 214 urines were collected, n=164 in Bangladesh and n=50 in Germany.

Neurobehavioral effects of exposure to propionic acid revisited-Does psychosocial stress interfere with distractive effects in volunteers?

Local irritants stimulate the nervous system via chemosensory pathways that trigger cognitive distraction, subjective complaints about impaired health, and physiological defense reflexes (e.g. eye-blinks).

Biomonitoring of concurrent exposure to ochratoxin A and citrinin in pregnant women in Bangladesh.

Ochratoxin A (OTA) and citrinin (CIT) are both nephrotoxic and teratogenic in animals, and the occurrence of these mycotoxins in food may cause adverse health effects in humans. Data on the combined exposure to these food contaminants are still scarce, especially in pregnancy. Therefore, a biomonitoring study was conducted to determine the presence of urinary biomarkers of exposure to OTA and CIT in pregnant women in Bangladesh.

Multidimensional assessment of self-reported chemical intolerance and its impact on chemosensory effects during ammonia exposure.

Purpose: Healthy individuals differ in self-reported chemical intolerance (CI). It is unclear whether this inter-individual variability impacts well-being and performance in environmental and occupational settings with chemical exposures. So far, operational definitions and questionnaires of CI have either emphasized physical symptoms or affective/behavioral disruption.