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| 2. |
- 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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| 3. |
- Yu, Han, et al.
(författare)
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Norfloxacin degradation by a green carbon black-Ti/SnO2-Sb electrochemical system in saline water
- 2019
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Ingår i: Catalysis Today. - : Elsevier BV. - 0920-5861. ; 327, s. 308-314
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Tidskriftsartikel (refereegranskat)abstract
- This work aims to degrade a typical antibiotic Norfloxacin (NOR) in saline water with a novel green carbon black based Ti/SnO2-Sb electrochemical catalysis system (TSSC), with Ti/SnO2-Sb as anode (TSSA) and a novel carbon black air diffusion electrode as cathode (CBAC). An electrochemical system with TSSA and a platinum carbon (Pt/C) cathode was used as control (TSSP). The removal ratio, degradation condition and the biodegradability were evaluated, the degradation pathway and mechanism were investigated. The result showed an efficient removal performance in both TSSC and TSSP systems. The removal ratio dropped with the lower current densities and higher initial pollutant loading. A considerable better removal performance was found in TSSC system, compared to that in TSSP system, when the low current density and saline concentration were applied. Meanwhile, 25.7% and 23.0% of COD removal ratios were obtained in TSSP and TSSC systems, respectively, in a short reaction time (25 min) and a very slight current density (0.18 mA cm−2). However, the TSSC showed a much more significant improvement of NOR biodegradability than that in TSSP system, indicating a considerable potential of TSSC system for both individual application and synergistic working with traditional biodegradation system for refractory antibiotics treatment.
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| 4. |
- Brenner, Darren R, et al.
(författare)
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Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia
- 2015
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 36:11, s. 1314-1326
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10−8) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10−7) and MTMR2 at 11q21 (rs10501831, P = 3.1×10−6) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10−7) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10−4 for KCNIP4, represented by rs9799795) and AC (P = 2.16×10−4 for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.
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| 5. |
- Guan, Jikui, et al.
(författare)
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FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
- 2015
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Ingår i: eLIFE. - Cambridge : eLife Sciences Publications. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild-type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor.
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| 6. |
- Ji, Xuemei, et al.
(författare)
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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
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| 7. |
- McKay, James D., et al.
(författare)
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Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
- 2017
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 49:7, s. 1126-1132
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Tidskriftsartikel (refereegranskat)abstract
- Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
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| 8. |
- Yu, Han, et al.
(författare)
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Energy-saving removal of methyl orange in high salinity wastewater by electrochemical oxidation via a novel Ti/SnO2-Sb anode-Air diffusion cathode system
- 2015
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Ingår i: Catalysis Today. - : Elsevier BV. - 0920-5861. ; 258, s. 156-161
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical oxidation is an effective method in removal of organic pollutant from high salinity waste-water (NaCl), by producing active chlorine at anode or hydrogen peroxide at cathode. To solve the existing problems including low efficiency, high cost and energy consumption, a Ti/SnO2-Sb anode (TSSA)-air diffusion cathode (TSSA-ADC) system was investigated for methyl orange (MO) removal from NaCl solution, using single TSSA system as control. The phase composition of TSSA was examined by X-ray diffraction. Accumulated concentrations of active chlorine, hydrogen peroxide, MO removal rate, TOC, pH value were recorded at different current densities. The results indicated that Sb-doped rutile SnO2 was formed on the TSSA. The TSSA and the ADC exhibited good catalysis to chlorine evolution and oxygen reduction, respectively. Although MO were almost completely removed in both systems, higher TOC removal, shorter running time and lower energy consumption were attained in the TSSA-ADC system. pH value was more stable (6.0-6.4) in the TSSA-ADC system than that in the TSSA system (6.0-9.4), predicting its stronger capacity in anti-scaling when treating high salinity wastewater with hard ions like Ca2+ and Mg2+. (C) 2015 Elsevier B.V. All rights reserved.
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| 9. |
- Yu, Han, et al.
(författare)
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Investigation and improvement of a novel double-working-electrode electrochemical system for organic matter treatment from high-salinity wastewater
- 2017
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Ingår i: Environmental Technology. - : Informa UK Limited. - 0959-3330 .- 1479-487X. ; 38:22, s. 2907-2915
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Tidskriftsartikel (refereegranskat)abstract
- The novel double-working-electrode electrochemical system with air diffusion cathode (ADC) and Ti/SnO2-Sb anode (TSSA) has shown higher efficiency and lower energy consumption for the degradation of organic pollutant from high-salinity wastewater, compared to the traditional single anode system. To further investigate and improve this system, in this work, firstly the effect of vital factors of the double-working-electrode electrochemical system including initial methyl orange (MO) concentration, NaCl concentration and initial pH value of organic solution were investigated, using MO as the targeted organic pollutant, carbon black ADC (CBAC) as cathode and stainless steel mesh electrode (SSME) as control. Besides, for the further improvement of removal performance, a novel home-made activated carbon-ADC (ACAC) was studied as cathode with the same investigation process. The results showed that, in the experiments studying the effect of both initial MO and NaCl concentrations, the removal performance was in the order of TSSA-ACAC > TSSA-CBAC > TSSA-SSME in all conditions of initial MO and NaCl concentrations. However, with the pH value reduced from 6.0 to 3.0, the performances of three systems turned to be much closer to each other. Besides, ACAC played a synergistic role in MO removal by greatly improving the MO removal performance and enhancing its adaptability to the reactor parametric variation. ACAC created a weak acidic environment for accelerating the indirect electro-oxidation of MO on TSSA. The MO degradation pathways in the three systems were the same but the TSSA-ACAC system gave a higher degradation kinetics order.
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| 10. |
- Zhu, Ying, et al.
(författare)
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Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer : A Mendelian Randomization Analysis
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:5, s. 935-942
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Tidskriftsartikel (refereegranskat)abstract
- Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall nonsmall cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.
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