| 1. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Figueroa, Jonine D., et al.
(författare)
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Genome-wide association study identifies multiple loci associated with bladder cancer risk
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:5, s. 1387-1398
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Tidskriftsartikel (refereegranskat)abstract
- andidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
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| 3. |
- Figueroa, Jonine D., et al.
(författare)
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Genome-wide interaction study of smoking and bladder cancer risk
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 35:8, s. 1737-1744
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Tidskriftsartikel (refereegranskat)abstract
- Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 x 10(-5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 x 10(-7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 x 10-7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
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| 4. |
- 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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| 5. |
- Rothman, Nathaniel, et al.
(författare)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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| 6. |
- Berntorp, Erik, et al.
(författare)
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Treatment of haemophilia A and B and von Willebrand's disease : summary and conclusions of a systematic review as part of a Swedish health-technology assessment
- 2012
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 18:2, s. 158-165
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Forskningsöversikt (refereegranskat)abstract
- In an ongoing health-technology assessment of haemophilia treatment in Sweden, performed by the governmental agency Dental and Pharmaceutical Benefits Agency (TLV; tandvårds-och läkemedelsförmånsverket), the Swedish Council on Health Technology Assessment (SBU; statens beredning för medicinsk utvärdering) was called upon to evaluate treatment of haemophilia A and B and von Willebrand's disease (VWD) with clotting factor concentrates. To evaluate the following questions: What are the short-term and long-term effects of different treatment strategies? What methods are available to treat haemophilia patients that have developed inhibitors against factor concentrates? Based on the questions addressed by the project, a systematic database search was conducted in PubMed, NHSEED, Cochrane Library, EMBASE and other relevant databases. The literature search covered all studies in the field published from 1985 up to the spring of 2010. In most instances, the scientific evidence is insufficient for the questions raised in the review. Concentrates of coagulation factors have good haemostatic effects on acute bleeding and surgical intervention in haemophilia A and B and VWD, but conclusions cannot be drawn about possible differences in the effects of different dosing strategies for acute bleeding and surgery. Prophylaxis initiated at a young age can prevent future joint damage in persons with haemophilia. The available treatment options for inhibitors have been insufficiently assessed. The economic consequences of various treatment regimens have been insufficiently analysed. Introduction of national and international registries is important.
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| 7. |
- Bosona, Techane, et al.
(författare)
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Assessing the Sustainability of Food Retail Business: The Case of Konsum Värmland, Sweden
- 2012
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Ingår i: Journal of Service Science and Management. - : Scientific Research Publishing, Inc.. - 1940-9893 .- 1940-9907. ; 5, s. 373-385
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Tidskriftsartikel (refereegranskat)abstract
- It is public concern that the impacts of food retail business activities need to be recognized and addressed properly. The main objective of this study was to assess the sustainable business management of a cooperative food retail business in Sweden, known as Konsum Värmland (KV). The necessary data and information on history and status of KV, and its practical activities concerning the implementation of sustainable development principles as well as the motivation and challenges encountered during the implementation were gathered via reviewing different documents, research papers and press releases; interviewing decision makers and other personnel in KV and other researchers who have investi- gated KV. The implementation of sustainability initiatives was analyzed in depth mainly based on triple bottom line sustainability theory. The findings indicate that KV has incorporated the sustainability issues into its mission and values. It practically has been implementing sustainability programs in environmental, social and economic dimensions. It pro- vides environmentally friendly and quality food products using its main brands names for local products. The major drives for KV to implement sustainability initiatives are leadership and employees' commitment, organizational core values, and members' and consumers' awareness. On the other hand, the major challenges to such sustainability initia- tives are high price of greener products, high logistics cost and emission due to long winter time, the seasonality of local product, and high cost of large scale investment.
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| 8. |
- Bosona, Techane, et al.
(författare)
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Box-Scheme Based Delivery System of Locally Produced Organic Food: Evaluation of Logistics Performance
- 2011
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Ingår i: Journal of Service Science and Management. - : Scientific Research Publishing, Inc.. - 1940-9893 .- 1940-9907. ; 4, s. 357-367
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Tidskriftsartikel (refereegranskat)abstract
- The local food systems such as fruit and vegetable box-schemes are gaining new profitable niche markets as the demand for local food is increasing. This paper presents the study made on box-scheme based local food supply system in Sweden, the Roslagslådan network, in which three distributors of locally produced organic food (LPOF) were the main actors. The objective of the study was to investigate the Roslagslådan LPOF supply network and evaluate its logistics performance. The study was based on literature review, interview, field measurement and route simulation and optimisation (in terms of route distance and driving time) analysis. The geographic information system (GIS) software was used to map the locations of the distributing companies and their delivery points (customer locations) while Route LogiX software was used for the simulation and optimisation analyses of routes for collection and distribution of LPOF, mainly vegetables and herb-based products. From the quantified information, the three companies distributed, on average about 134 boxes of LPOF to about 116 delivery points, once in two weeks period mainly during August-October. The distribution via Roslagslådan network was supplemented with other means of selling: on farm sale, open market sales and selling via supermarket. The route optimisation analysis resulted in significant savings in route distance and delivery time. The savings in distance were up to 76%, 23% and 32% for Company-1, Company-2 and Company-3 respectively while the corresponding savings in delivery time were up to 75%, 10% and 16%. This reduction in distance and time led to positive improvement toward the environmental and economical issues enhancing the sustainability of local food systems
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| 9. |
- Bosona, Techane, et al.
(författare)
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GIS-Based Analysis of Integrated Food Distribution Network in Local Food Supply Chain
- 2013
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Ingår i: International Journal of Business and Management. - : Canadian Center of Science and Education. - 1833-3850 .- 1833-8119. ; 8, s. 13-34
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Tidskriftsartikel (refereegranskat)abstract
- Local food producers need to integrate within networks of suppliers, distributor, customers and communityrepresentatives in order to increase their competitiveness. The main objective of this study was to evaluate theperformance of an integrated food distribution network (IFDN) in Sweden. Location and route analyses wereconducted using data of 11 producers, 149 customers and one distribution centre (DC). Geographic InformationSystem (GIS) tools and location analysis techniques were utilized. Route analyses were done considering onenon-integrated distribution system (scenario1) and three different integrated distributions systems (scenarios 2, 3and 4). The results of location analysis indicated that the existing DC is located at best position. When comparedto Scenario1, best improvements were gained in scenario3 i.e. up to 64% in number of routes, 53% in number ofvisits, 74% in transport distance and 63% in transport time. As a consequence, the emissions emanated fromvehicles were reduced. The analyses gave insights into main implications of IFDN such as implication forlogistics efficiency; implication for food and service quality; and implication for environmental sustainability oflocal food supply chain.
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| 10. |
- Bosona, Techane, et al.
(författare)
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Integrated logistics network for the supply chain of locally produced food, Part I: Location and route optimization analyses
- 2011
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Ingår i: Journal of Service Science and Management. - : Scientific Research Publishing, Inc.. - 1940-9893 .- 1940-9907. ; 4, s. 174-183
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Tidskriftsartikel (refereegranskat)abstract
- Due to a growing interest in locally produced food (LPF), there is a tendency of promoting local food systems. The objective of this study was to investigate the existing flow of LPF from producers to consumers and develop a coordinated and efficient distribution system for producers in Halland region, Sweden. An integrated logistics network (ILN) embracing producers, retailers, a collection centre (CC) and a distribution centre (DC) was proposed. Data collection, location analysis and route optimisation analysis were conducted. Geographic information system (GIS) and Route LogiX software were utilised for the analyses. Four scenarios of food distribution were identified and analyzed. When compared to the existing system, the best scenario improved transport distance, time and number of routes up to 93%, 92% and 87% respectively. The distribution of LPF was integrated into large scale food distribution channel (LSFDC) and this could increase the sustainability of local food system
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