| 51. |
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| 52. |
- Fu, Yi-Ping, et al.
(författare)
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The 19q12 Bladder Cancer GWAS Signal : Association with Cyclin E Function and Aggressive Disease
- 2014
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818
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Tidskriftsartikel (refereegranskat)abstract
- A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
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| 53. |
- Harrad, Stuart, et al.
(författare)
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Indoor Contamination with Hexabromocyclododecanes, Polybrominated Diphenyl Ethers, and Perfluoroalkyl Compounds : An Important Exposure Pathway for People?
- 2010
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:9, s. 3221-3231
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Forskningsöversikt (refereegranskat)abstract
- This review underlines the importance of indoor contamination as a pathway of human exposure to hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs), and perfluoroalkyl compounds (PFCs). There is ample evidence of substantial contamination of indoor dust with these chemicals and that their concentrations in indoor air exceed substantially those outdoors. Studies examining the relationship between body burden and exposure via indoor dust are inconsistent while some indicate a link between body burdens and PBDE and HBCD exposure via dust ingestion, others find no correlation. Likewise, while concentrations in indoor dust and human tissues are both highly skewed, this does not necessarily imply causality. Evidence suggests exposure via dust ingestion is higher for toddlers than adults. Research priorities include identifying means of reducing indoor concentrations and indoor monitoring methods that provide the most ""biologically-relevant"" measures of exposure as well as monitoring a wider range of microenvironment categories. Other gaps include studies to improve understanding of the following: emission rates and mechanisms via which these contaminants migrate from products into indoor air and dust; relationships between indoor exposures and human body burdens; relevant physicochemical properties; the gastrointestinal uptake by humans of these chemicals from indoor dust; and human dust ingestion rates.
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| 54. |
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| 55. |
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| 56. |
- Lohmann, Rainer, et al.
(författare)
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Passive-sampler-derived PCB and OCP concentrations in the waters of the world : first results from the AQUA-GAPS/MONET network
- 2023
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:25, s. 9342-9352
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are recognized as pollutants of global concern, but so far, information on the trends of legacy POPs in the waters of the world has been missing due to logistical, analytical, and financial reasons. Passive samplers have emerged as an attractive alternative to active water sampling methods as they accumulate POPs, represent time-weighted average concentrations, and can easily be shipped and deployed. As part of the AQUA-GAPS/MONET, passive samplers were deployed at 40 globally distributed sites between 2016 and 2020, for a total of 21 freshwater and 40 marine deployments. Results from silicone passive samplers showed α-hexachlorocyclohexane (HCH) and γ-HCH displaying the greatest concentrations in the northern latitudes/Arctic Ocean, in stark contrast to the more persistent penta (PeCB)- and hexachlorobenzene (HCB), which approached equilibrium across sampling sites. Geospatial patterns of polychlorinated biphenyl (PCB) aqueous concentrations closely matched original estimates of production and use, implying limited global transport. Positive correlations between log-transformed concentrations of Σ7PCB, ΣDDTs, Σendosulfan, and Σchlordane, but not ΣHCH, and the log of population density (p < 0.05) within 5 and 10 km of the sampling sites also supported limited transport from used sites. These results help to understand the extent of global distribution, and eventually time-trends, of organic pollutants in aquatic systems, such as across freshwaters and oceans. Future deployments will aim to establish time-trends at selected sites while adding to the geographical coverage.
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| 57. |
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