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  • 1
    Keywords: POPULATION ; METABOLISM ; CARCINOGENESIS ; mechanisms ; HEALTH ; METHYLATION ; PERSPECTIVE ; TOXICOLOGY ; BASAL-CELL CARCINOMA ; BANGLADESH
    Abstract: Occupational studies show a high risk of lung cancer related to arsenic exposure by inhalation; however, only a few studies, and with conflicting results, previously examined a potential link between arsenic exposure at work and skin cancer. The aim of this study is to assess airborne arsenic exposures at the workplace and to quantify associations with nonmelanoma skin cancer (NMSC). The study sample consists of 618 incident cases of NMSC and 527 hospital-based controls aged 30-79 years from Hungary, Romania and Slovakia. Exposures were evaluated by local experts using occupational histories. Information on host factors and other exposures was collected and used to adjust the associations of interest using multivariable logistic regression. The lifetime prevalence of exposure to work-related arsenic is 23.9% for cases and 15.5% for controls. No significant association between arsenic exposure in the workplace and NMSC was detected, although an increased adjusted odd ratio was observed for participants with higher cumulative lifetime workplace exposure to arsenic in dust and fumes compared to referents [odds ratios (OR) = 1.94, 95% confidence interval (CI) = 0.76-4.95]. There is evidence for modification of the workplace arsenic-NMSC association by work-related sunlight exposure in women, with a markedly increased adjusted OR in the presence of workplace sunlight exposure (OR = 10.22, 95% CI = 2.48-42.07). Workplace coexposure to arsenic and sunlight may thus pose an increased risk of NMSC.
    Type of Publication: Journal article published
    PubMed ID: 23595521
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  • 2
    Keywords: human ; EXPOSURE ; RISK ; METABOLITES ; SWEDEN ; MASS-SPECTROMETRY ; INDIVIDUALS ; SMOKERS ; DRINKING-WATER ; SPECIATION ; CONTAMINATION ; URINARY-EXCRETION ; ARSENOSUGAR ; INGESTION ; RICE
    Abstract: Inorganic arsenic is a potent human carcinogen and toxicant which people are exposed to mainly via drinking water and food. The objective of the present study was to assess current exposure to arsenic via drinking water in three European countries. For this purpose, 520 individuals from four Hungarian, two Slovakian and two Romanian countries were investigated by measuring inorganic arsenic and methylated arsenic metabolites in urine by high performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry. Arsenic in drinking water was determined by atomic absorption spectrometry. Significantly higher concentrations of arsenic were found in both the water and the urine samples from the Hungarian counties (median: 11 and 15 mu g dm(-3), respectively; p 〈 0.001) than from the Slovakian (median: 0.94 and 4.5 mu g dm(-3), respectively) and Romanian (median: 0.70 and 2.1 mu g dm(-3), respectively) counties. A significant correlation was seen between arsenic in water and arsenic in urine (R-2 = 0.46). At low water arsenic concentrations, the relative amount of dimethylarsinic acid (DMA) in urine was increased, indicating exposure via food. Also, high body mass index was associated with higher concentrations of arsenic in urine (p = 0.03), mostly in the form of DMA. Smokers had significantly higher urinary arsenic concentrations than non-smokers (p = 0.03). In conclusion, elevated arsenic exposure via drinking water was prevalent in some of the counties. Exposure to arsenic from food, mainly as DMA, and cigarette smoke, mainly as inorganic arsenic, are major determinants of arsenic exposure at very low concentrations of arsenic in drinking water
    Type of Publication: Journal article published
    PubMed ID: 16395480
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  • 3
    Keywords: CANCER ; carcinoma ; Germany ; EXPOSURE ; RISK ; GENE ; GENES ; radiation ; DNA ; SKIN ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; VARIANTS ; BREAST-CANCER ; IN-SITU ; AGE ; WOMEN ; DNA-REPAIR ; REPAIR ; MEN ; MODULATION ; cancer risk ; DAMAGE ; DNA repair ; basal cell carcinoma ; molecular epidemiology ; CELL CARCINOMA ; RE ; VARIANT ; DRINKING-WATER ; SINGLE NUCLEOTIDE POLYMORPHISMS ; INTERVAL ; single-nucleotide ; multiple testing ; CANCER-RISK ; STRAND BREAKS ; EXPOSURES ; CONTAMINATION ; SUN EXPOSURE
    Abstract: In addition to environmental exposures like UV radiation and, in some cases, arsenic contamination of drinking water, genetic factors may also influence the individual susceptibility to basal cell carcinoma of skin (BCC). In the present study, 529 cases diagnosed with BCC and 533 controls from Hungary, Romania and Slovakia were genotyped for one polymorphism in each of seven DNA repair genes. The variant allele for T241M (C 〉 T) polymorphism in the XRCC3 gene was associated with a decreased cancer risk [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.61-0.88; P = 0.0007, multiple testing corrected P = 0.0041. The risk of multiple BCC was significantly lower among variant allele carriers than in noncarriers (P = 0.04). Men homozygous for the C-allele for E185Q (G 〉 C) polymorphism in the NBS1 gene showed an increased BCC risk (OR, 2.19; 95% CI, 1.23-3.91), but not women (OR, 0.84; 95 % CI, 0.49-1.47). In men, the age and nationality adjusted OR for the genotype CC (XRCC3)/CC (NBS1) was 8.79 (95% CI, 2.10-36.8), compared with the genotype TT (XRCC3)/GG (NBS1). The data from this study show overall risk modulation of BCC by variant allele for T241M polymorphism in XRCC3 and gender-specific effect by E185Q polymorphism in NBS1
    Type of Publication: Journal article published
    PubMed ID: 16501254
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  • 4
    Keywords: BLOOD ; human ; GENERATION ; POPULATION ; GENE ; EFFICIENCY ; METABOLISM ; INDEX ; REDUCTION ; GENETIC POLYMORPHISMS ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; METABOLITES ; HEALTH ; DIFFERENCE ; GLUTATHIONE ; PLASMA ; AGE ; WOMEN ; MEN ; mass spectrometry ; SWEDEN ; MASS-SPECTROMETRY ; US ; genetic polymorphism ; INDIVIDUALS ; LIQUID-CHROMATOGRAPHY ; BODY ; METHYLATION ; SKIN-CANCER ; URINE ; glutathione-S-transferase ; METABOLITE ; MASS INDEX ; MASSES ; BODIES ; RE ; arsenic ; DRINKING-WATER ; CAPACITY ; METHYLTRANSFERASE ; WEIGHT ; METHYLENETETRAHYDROFOLATE REDUCTASE ; MTHFR ; methods ; MASS ; OVERWEIGHT ; USA ; HUMAN-CELLS ; METHYLTRANSFERASES ; female ; Male ; WHOLE-BLOOD ; PUBLIC-HEALTH ; steroids ; BODY-MASS ; BODY-MASS-INDEX ; sex ; body mass ; AS3MT ; BLADDER-CANCER RISK ; GSTO1 ; HUMAN URINE ; METHYLATION CAPABILITY ; MMA(V) REDUCTASE ; MONOMETHYLARSONOUS ACID MMA(III) ; WEST-BENGAL
    Abstract: BACKGROUND: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. OBJECTIVES: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. METHODS: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3M7), glutathione S-transferase omega 1 (GSTO1), and methylenetetrahydrofolate reductase (MTHFR). RESULTS: The results show that the M287T (T -〉 C) polymorphism in the AS3MT gene, the A222V (C -〉 T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 mu g/L arsenic in urine. Females 〈 60 years of age had, in general, higher methylation efficiency than males, indicating an influence of sex steroids. That might also explain the observed better methylation in overweight or obese women, compared with normal weight men. The influence of the M287T (T -〉 C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. CONCLUSIONS: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic
    Type of Publication: Journal article published
    PubMed ID: 17637926
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  • 5
    Keywords: mechanisms ; SUSCEPTIBILITY ; VARIANTS ; SINGLE NUCLEOTIDE POLYMORPHISMS ; METAANALYSIS ; BASAL-CELL CARCINOMA ; SUN EXPOSURE ; ULTRAVIOLET-RADIATION ; GENOME-WIDE ASSOCIATION ; SLOVAKIA
    Abstract: X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3) polymorphisms are relatively frequent in Caucasian populations and may have implications in skin cancer modulation. A few studies have evaluated their association with non-melanoma skin cancer (NMSC), but the results are inconsistent. In the current study, we aim to assess the impact of XRCC1 R399Q and XRCC3 T241M polymorphisms on the risk of NMSC associated with sunlight and arsenic exposure. Study participants consist of 618 new cases of NMSC and 527 hospital-based controls frequency matched on age, sex, and county of residence from Hungary, Romania, and Slovakia. Adjusted effects are estimated using multivariable logistic regression. The results indicate an increased risk of squamous cell carcinoma (SCC) for the homozygous variant genotype of XRCC1 R399Q (OR 2.53, 95% CI 1.14-5.65) and a protective effect against basal cell carcinoma (BCC) for the homozygous variant genotype of XRCC3 T241M (OR 0.61, 95% CI 0.41-0.92), compared with the respective homozygous common genotypes. Significant interactions are detected between XRCC3 T241M and sunlight exposure at work, and between XRCC3 T241M and exposure to arsenic in drinking water (p-value for interaction 〈0.10). In conclusion, the current study demonstrates that polymorphisms in XRCC genes may modify the associations between skin cancer risk and exposure to sunlight or arsenic. Given the high prevalence of genetic polymorphisms modifying the association between exposure to environmental carcinogens and NMSC, these results are of substantial relevance to public health.
    Type of Publication: Journal article published
    PubMed ID: 25218703
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  • 6
    Keywords: EXPOSURE ; POLYMORPHISMS ; BLADDER-CANCER ; METHYLATION ; SKIN-CANCER ; UROTHELIAL CARCINOMA ; GENOTYPE ; PROFILE ; HUNGARY ; SLOVAKIA
    Abstract: Exposure to inorganic arsenic increases the risk of basal cell carcinoma (BCC). Arsenic metabolism is a susceptibility factor for arsenic toxicity, and specific haplotypes in arsenic (+3 oxidation state) methyltransferase (AS3MT) have been associated with increased urinary fractions of the most toxic arsenic metabolite, methylarsonic acid (MMA). The aim of this study is to elucidate the association of AS3MT haplotypes with arsenic metabolism and the risk of BCC. Four AS3MT polymorphisms were genotyped in BCC cases (N=529) and controls (N=533) from Eastern Europe with low to moderate arsenic exposure (lifetime average drinking water concentration: 1.3 mu g/L, range 0.01-167 mu g/L). Urinary metabolites [inorganic arsenic (iAs), MMA, dimethylarsinic acid (DMA)] were analyzed by HPLC-ICPMS. Five AS3MT haplotypes (based on rs3740400 A/C, rs3740393 G/C, rs11191439 T/C and rs1046778 T/C) had frequencies 〉5%. Individuals with the CCTC haplotype had lower %iAs (P=0.032) and %MMA (P=0.020) in urine, and higher %DMA (P=0.033); individuals with the CGCT haplotype had higher %MMA (P〈0.001) and lower %DMA (P〈0.001). All haplotypes showed increased risk of BCC with increasing arsenic exposure through drinking water (ORs 1.1-1.4, P values from 〈0.001 to 0.082), except for the CCTC haplotype (OR 1.0, CI 0.9-1.2, P value 0.85). The results suggest that carriage of AS3MT haplotypes associated with less-efficient arsenic methylation, or lack of AS3MT haplotypes associated with a more-efficient arsenic methylation, results in higher risk of arsenic-related BCC. The fact that AS3MT haplotype status modified arsenic metabolism, and in turn the arsenic-related BCC risk, supports a causal relationship between low-level arsenic exposure and BCC. Environ. Mol. Mutagen. 56:60-69, 2015.
    Type of Publication: Journal article published
    PubMed ID: 25156000
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  • 7
    Abstract: OBJECTIVE: Methods and results are presented for an arsenic exposure assessment integral to an epidemiological case-control study of arsenic and cancer-the European Commission funded ASHRAM (Arsenic Health Risk Assessment and Molecular Epidemiology) study carried out in some counties of Hungary, Romania and Slovakia. METHODS: The exposure history of each participant (N = 1,392) was constructed by taking into account how much water they consumed (as water, in drinks and in food), sources of drinking water in their various residences over their lifetime, and the concentrations of arsenic in their various water supplies measured by Hydride Generation-Atomic Absorption Spectrometry (HG-AAS). Concentrations of arsenic in previous water supplies were either derived from contemporary analyses of the same source, or from routine historical data from measurements performed by the authorities in each country. Using this approach, 80% of the recorded lifetime residential history was matched to an arsenic concentration. Seven indices of current, life time, and peak exposure were calculated. RESULTS: The exposure indices were all log-normally distributed and the mean and median lifetime average concentrations were in Hungary 14.7 and 13.3 microg l(-1), Romania 3.8 and 0.7 microg l(-1) and in Slovakia 1.9 and 0.8 microg l(-1), respectively. Overall 25% of the population had average concentrations over 10 microg l(-1) and 8% with exposure over 50 microg l(-1). CONCLUSIONS: Careful assessment of arsenic in drinking water supplies (both current and previous) enabled the majority of study participants' cumulative lifetime of potential exposure to arsenic in residential water to be characterised.
    Type of Publication: Journal article published
    PubMed ID: 20401490
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  • 8
    Keywords: CANCER ; carcinoma ; EPIDEMIOLOGY ; GENE-EXPRESSION ; METABOLISM ; SELECTION ; HUMAN EPIDERMAL-KERATINOCYTES ; METHYLATION ; URINE ; DRINKING-WATER ; Skin Neoplasms ; MALIGNANT NEOPLASMS ; TAIWAN ; BLACKFOOT DISEASE ; ENDEMIC AREA ; low-dose arsenic ; SKIN-CANCER RISK ; WELL WATER
    Abstract: BACKGROUND: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations 〈 100 mu g/L in drinking water. OBJECTIVES: We aimed to quantify skin cancer relative risks in relation to iAs exposure 〈 100 mu g/L and the modifying effects of iAs metabolism. METHODS: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case-control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression. RESULTS: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-mu g/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA. CONCLUSION: We found a positive association between BCC and exposure to iAs through drinking water with concentrations 〈 100 mu g/L
    Type of Publication: Journal article published
    PubMed ID: 22436128
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  • 9
    Keywords: DISEASE ; EPIDEMIOLOGY ; BREAST ; SUNLIGHT ; CELL CARCINOMA ; LIGHT ; SUN ; VITAMIN-D
    Abstract: BACKGROUND: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation. OBJECTIVES: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. METHODS: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. RESULTS: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27-0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure. CONCLUSIONS: The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.
    Type of Publication: Journal article published
    PubMed ID: 23638051
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  • 10
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract A capillary blood microsampling technique was tested among urban young children in Stockholm. Blood lead (BPb) and hemoglobin (Hb) concentrations were determined in capillary blood obtained by fingerstick from 41 children, 13–20 months old, and the accompanying parent. The quality control included control for lead (Pb) and cadmium (Cd) contamination of material and equipment used for blood sampling, washing procedures for the hands and fingers to be punctured, comparisons of Pb and Cd concentrations in blood obtained by fingerstick and by brachial vein puncture from the same individuals, analysis of external quality control samples for Pb and Cd in blood together with the collected samples, and evaluation of the analytical performance using linear regression analysis. The results showed that blood sampling material may contaminate the blood samples with amounts of Pb and Cd that would seriously influence the monitoring results in the low concentration range (〈100 μg Pb/L and 〈1 μg Cd/L). However, it is possible to obtain reliable BPb concentrations (〉10 μg Pb/L), but not BCd concentrations (〈1 μg Cd/L), with the capillary blood microsampling technique tested provided that a strict quality control is applied. The sampling procedure tested was well accepted by the children and their parents. The children's median BPb concentration (27 μg/L; range 9–73 μg/L) was similar to the median BPb concentration of their parents (27 μg/L; range 7–74 μg/L). However, the correlation between child and parent BPb concentrations was poor (R2=0.20), which may indicate different sources to Pb exposure in children and parents.
    Type of Medium: Electronic Resource
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