| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 3. |
- Cao, Huiming, et al.
(författare)
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Effect of Enterohepatic Circulation on the Accumulation of Per- and Polyfluoroalkyl Substances : Evidence from Experimental and Computational Studies
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:5, s. 3214-3224
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetic characteristics of per- and polyfluoroalkyl substances (PFAS) affect their distribution and bioaccumulation in biological systems. The enterohepatic circulation leads to reabsorption of certain chemicals from bile back into blood and the liver and thus influences their elimination, yet its influence on PFAS bioaccumulation remains unclear. We explored the role of enterohepatic circulation in PFAS bioaccumulation by examining tissue distribution of various PFAS in wild fish and a rat model. Computational models were used to determine the reabsorbed fractions of PFAS by calculating binding affinities of PFAS for key transporter proteins of enterohepatic circulation. The results indicated that higher concentrations were observed in blood, the liver, and bile compared to other tissues for some PFAS in fish. Furthermore, exposure to a PFAS mixture on the rat model showed that the reabsorption phenomenon appeared during 8-12 h for most long-chain PFAS. Molecular docking calculations suggest that PFAS can bind to key transporter proteins via electrostatic and hydrophobic interactions. Further regression analysis adds support to the hypothesis that binding affinity of the apical sodium-dependent bile acid transporter is the most important variable to predict the human half-lives of PFAS. This study demonstrated the critical role of enterohepatic circulation in reabsorption, distribution, and accumulation of PFAS.
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| 4. |
- Cao, Huiming, et al.
(författare)
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Screening of Potential PFOS Alternatives To Decrease Liver Bioaccumulation : Experimental and Computational Approaches
- 2019
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:5, s. 2811-2819
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant with significant bioaccumulation potential in liver tissues. Exposure to PFOS could cause increase of liver weight, induce adenomas of the liver, and cause hepatomegaly. Alternatives of PFOS might be designed and synthesized that have significantly lower liver bioaccumulation. In this study, we conducted animal exposure experiments to investigate tissue accumulations of 14 per- and polyfluoroalkyl substances. Correlation analysis demonstrated that accumulation of the compounds in rat liver had strong correlations with their binding affinities of liver fatty acid binding protein (LFABP). Thus, we combined a quantitative structure-activity relationship model with molecular dynamics (MD) simulations to develop computational models to predict the LFABP binding affinities of two newly synthesized alternatives, perfluorodecalin-2-sulfonic acid and N-diperfluorobutanoic acid. The binding characteristics of the PFOS alternatives for LFABP were elaborated to explore how the different structural modifications of molecules influenced the underlying binding mechanisms. Subsequent animal experiments demonstrated that the binding free energy calculations based on the MD simulations provided a good indicator to reflect the relative degree of liver accumulation of the PFOS alternatives in the same exposure doses and durations. Our findings from the combination of experimental exposure and computational model can provide helpful information to design potential alternatives of PFOS with weak LFABP binding capability and low liver accumulation.
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| 5. |
- Fu, Jianjie, et al.
(författare)
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Temporal trends (2005-2009) of PCDD/Fs, PCBs, PBDEs in rice hulls from an e-waste dismantling area after stricter environmental regulations
- 2012
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 88:3, s. 330-335
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Tidskriftsartikel (refereegranskat)abstract
- Primitive e-waste dismantling activities have been of increasing concern due to serious environmental and human health problems, and therefore authorities in China have strengthened the regulations on illegal e-waste recycling activities. In this work, we used rice hull as a passive sampler and investigated temporal trends of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) in areas near e-waste recycling sites after the stricter regulations. Furthermore, the distribution patterns and composition profiles of these contaminants were also discussed. The average concentrations of the three groups of persistent organic pollutants (POPs) in rice hulls have markedly decreased during the period of 2005-2009. Specifically, from 12.9 (average value in 2005) to 0.37 pg WHO-TEQ/g (dry weight, dw) (in 2009) for PCDD/Fs, 47.6 (2005) to 7.10 ng g(-1)dw (2009) for PCBs, and 2.51 (2005) to 0.89 ng g(-1), dw (2009) for PBDEs. The significant decrease of combustion markers 2,3,4,7,8-PeCDF, 1,2,3,6,7,8HxCDF and PCB126, and the PCDD/PCDF ratio from 1:9 (2005) to 7:3 (2009) is likely a result of stricter regulations on open combustion activities. This study suggests that stricter control measures, strengthened laws and regulations and more environmental friendly techniques could be effective measures in reducing the release and formation of related POPs in typical e-waste dismantling sites, and these measures could further improve the quality of the environment and health of the local inhabitants.
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| 6. |
- Hao, Yanfen, et al.
(författare)
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Air monitoring of polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides in West Antarctica during 2011-2017 : Concentrations, temporal trends and potential sources
- 2019
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 249, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- Annual air samples were collected at various sites in the Fildes Peninsula, West Antarctica from December 2010 to January 2018 using XAD-2 resin passive air samplers to investigate concentrations, temporal trends and potential sources of persistent organic pollutants (POPs) in Antarctic air. Relatively low concentrations of polychlorinated biphenyls (PCBs) (Σ19PCBs: 1.5-29.7 pg/m3), polybrominated diphenyl ethers (PBDEs) (Σ12PBDEs: 0.2-2.9 pg/m3) and organochlorine pesticides (OCPs) (Σ13OCPs: 101-278 pg/m3) were found in the atmosphere of West Antarctica. PCB-11, BDE-47 and hexachlorobenzene (HCB) were the predominant compounds in the atmosphere. The concentrations of PCBs, HCHs, DDTs and endosulfans were found to show decreasing temporal trends, whereas uniform temporal trends were observed for HCB. The atmospheric half-life values for PCBs, HCHs, DDTs and endosulfans in Antarctic air were estimated for the first time, using regressions of the natural logarithm of the concentrations versus the number of years, obtaining the values of 2.0, 2.0, 2.4 and 1.2 year, respectively. An increasing ratio of α-HCH/γ-HCH indicated long residence time for α-HCH and possible transformation of γ-HCH to α-HCH in the atmosphere. The ratios of p,p'-DDT/p,p'-DDE were mostly lower than unity in this study, which could be attributed to aged sources. It was found that long-range atmospheric transport was still considered to be the main contributing factor to the atmospheric levels of the POPs in West Antarctica whereas the contribution of human activities at the Chinese Great Wall Station was minor. The results of this study give a view on the most recent temporal trends and provide new insights regarding the occurrence of various POPs in the Antarctic atmosphere.
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| 7. |
- Li, Honghua, et al.
(författare)
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Levels and distribution of hexabromocyclododecane (HBCD) in environmental samples near manufacturing facilities in Laizhou Bay area, East China
- 2012
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Ingår i: Journal of Environmental Monitoring. - : Royal Society of Chemistry (RSC). - 1464-0325 .- 1464-0333. ; 14:10, s. 2591-2597
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Tidskriftsartikel (refereegranskat)abstract
- A total of 55 samples including soil, sediment, plants (cypress, reed and seepweed) and aquatic species were collected at locations around hexabromocyclododecane (HBCD) manufacturing facilities in Laizhou Bay area, East China. HBCD was determined at concentrations ranging between 0.88 and 6901 ng g(-1) dry weight (dw), 2.93-1029 ng g(-1) dw, 8.88-160241 ng g(-1) dw, and 7.09-815 ng g(-1) lipid weight (lw), respectively. Significant negative correlations (r(2) = 0.54, p = 0.006) were observed between HBCD concentrations in soils and the distance from the manufacturing facility, and the concentrations became constant when the distance was >4 km. The calculation results on the bioaccumulation factors (BAFs) suggested that HBCD may be accumulated in plants. Tissue-specific bioaccumulation of HBCD diastereoisomers was found in aquatic species. For example, in crabs the highest concentrations of HBCD (815 ng g(-1) lw for female and 446 ng g(-1) lw for male) were observed in the gill. Besides the gill, α-HBCD was more preferentially accumulated in the spermary and ovary, while β- and γ-HBCD were more accumulated in the muscle. A similar distribution was also observed in roe and muscle of goby fish.
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| 8. |
- Li, Yingming, et al.
(författare)
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Levels and vertical distributions of PCBs, PBDEs, and OCPs in the atmospheric boundary layer : observation from the Beijing 325-m meteorological tower
- 2009
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:4, s. 1030-1035
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Tidskriftsartikel (refereegranskat)abstract
- Polyurethane foam disk passive air sampling was carried out to investigate the levels, vertical distributions, and potential sources of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs) in the atmospheric boundary layer of an urban site in Asia. Sampling was performed at nine heights (15, 47, 80, 120, 160, 200, 240, 280, 320 m) of the 325-m meteorological tower in Beijing, China over three 2-month periods between December 2006 and August 2007. This is the first study to report vertical variations of PBDEs in the ABL and one of only a few studies to investigate vertical distributions of persistent organic pollutants. The levels of sigma19PCBs and sigma8PBDEs were relatively low, ranging from 22 to 65 and from 2.3 to 18 pg m-3, respectively. Air concentrations of gamma-HCH were high, with values in the range of 39-103 pg m-3 in winter, 100-180 pg m-3 in spring, and 115-242 pg m-3 in summer, respectively. alpha-HCH concentrations ranged from 20 to 86 pg m-3, p,p'-DDT between 7.3 and 78 pg m-3, and HCB between 15 and 160 pg m-3. The seasonal variations of PCBs, PBDEs, and OCPs may reflect different sources for these chemicals, such as those related with regional use (gamma-HCH), volatilization/re-emission (PBDEs, PCBs, alpha-HCH), and pesticide impurities (HCB). Although the performance reference compounds (PRCs) were spiked before deployment, the sampling rates showed strong dependency on wind speeds, resulting in large variations in uptake rates in the ABL, ranging from approximately 7.0 m3 day-1 at ground level to 11 m3 day-1 at 320 m. Levels of PCBs, PBDEs, and OCPs decreased with increasing ABL height indicating the potential of Beijing as the local sources.
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| 9. |
- Li, Yingming, et al.
(författare)
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Reduction of atmospheric polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during the 2008 Beijing Olympic games
- 2011
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 45:8, s. 3304-3309
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Tidskriftsartikel (refereegranskat)abstract
- A total of 120 air samples were collected at three urban and one rural location in Beijing, China in the summers of 2007-2010, and before, during, and after the Beijing 2008 Olympic Games (BOG), in order to assess the effectiveness of long-term and short-term emission-control measures in reducing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the atmosphere. During the BOG (August, 2008), the PCDD/Fs concentrations decreased to an average value of 1150 fg m−3 (63 fg I-TEQ m−3), which was reduced by approximately 70% from the average in 2007 and by 29% from that in July 2008, before the Olympic event began. Although 2009-2010 levels of PCDD/Fs were significantly higher than 2008, the overall temporal trend was decreasing for summer months during the sampling campaign period. The apparent half-lives of atmospheric PCDD/Fs were estimated to be 3.2-5.8 years by statistically regressing the logarithm PCDD/Fs concentrations versus the number of years passed since 2006. The air concentrations of total suspended particulates (TSP) during the BOG ranged between 135 and 183 μg m−3, showing a 52% reduction from 2007 and 26% decrease from those prior to the Olympic event. No significant relationships were found between meteorological parameters (temperature, humidity, and wind speed) and PCDD/Fs or TSP during the BOG, whereas the PCDD/Fs concentrations were significantly dependent on the air quality (p < 0.05, positive against TSP and negative against visibility). This work is one of few temporal trend studies of atmospheric PCDD/Fs in mainland China, and provides unique insight into the effects of large-scale control measures in improving air quality and reducing one of the most ubiquitous and toxic organic pollutants in the environment.
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| 10. |
- Ruan, Ting, et al.
(författare)
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Concentrations and composition profiles of benzotriazole UV stabilizers in municipal sewage sludge in China
- 2012
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 46:4, s. 2071-2079
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Tidskriftsartikel (refereegranskat)abstract
- The environmental contamination and fate of benzotriazole UV stabilizers (BZTs) have received increasing attention due to their large production volume and wide usage in various consumer and industrial products. In the present work, 60 municipal sewage sludge samples from wastewater treatment plants (WWTPs) in 33 cities in China were collected to investigate the occurrence and distribution of 9 frequently used BZTs. The most dominant analogue was 2-[3,5-bis(1-methyl-1-phenylethyl)-2-hydroxyphenyl]benzotriazole (UV-234) at a median concentration of 116 ng/g (dry weight) and accounted on average for 27.2% of total BZTs. The abundance was successively followed by 2-(2-hydroxy-5-tert-octylphenyl)benzotriazole (UV-329, average 24.3%), 2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chlorobenzotriazole (UV-326, average 22.2%), 2-(3,5-di-tert-amyl-2-hydroxyphenyl)benzotriazole (UV-328, average 17.7%), and 2-(2-hydroxy-5-methylphenyl)benzotriazole (UV-P, average 6.6%), with median concentrations of 66.8, 67.8, 57.3, and 20.6 ng/g, respectively. 5-Chloro-2-(3,5-di-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-327) and 2-(3-sec-butyl-5-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-350) had low detection frequency, while 2-(3,5-di-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-320) and 2-(5-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-PS) were not detectable in any sample. To our knowledge, this is the first study reporting the occurrence of UV-234, UV-329, and UV-350 in sewage sludge in China. Significant correlations were found among the BZT concentrations and also with a WWTP characteristic (daily treatment volume). Furthermore, results from degradation prediction and multimedia fate simulation based on a quantitative structure-property relationship (QSPR) model at screening level also implied that the commercial BZT chemicals and their plausible transformation products might be persistent in the environment.
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