| 1. |
- Tjonneland, Anne, et al.
(författare)
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Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2007
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 18:4, s. 361-373
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Tidskriftsartikel (refereegranskat)abstract
- Objective Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer. Methods Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors. Results During 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35-75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01-1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate. Conclusion This large European study supports previous findings that recent alcohol intake increases the risk of breast cancer.
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| 2. |
- Gudmundsdottir, Valborg, et al.
(författare)
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Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study
- 2020
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.Methods: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.Results: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.Conclusions: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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| 3. |
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| 4. |
- Heuer, Rolf-Dieter, et al.
(författare)
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Ex post evaluation of the activities of the joint research centre under Horizon 2020 and Euratom 2014-2020
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The report is the result of the external Panel ex post evaluation of the JRC activities under H2020 and Euratom 2014-2020. It provides the independent assessment requested in the Council Decisions concerning the specific programmes to be carried out by means of direct actions by the Joint Research Centre implementing the Horizon 2020 Framework Programme (2014-2020) of the European Commission and of the European Atomic Energy Community (Euratom). The evaluation has been conducted by a panel of independent external experts under the chairmanship of Dr Rolf-Dieter Heuer. In this report the Panel concludes positively on the effectiveness of the JRC as the Commission’s science service in support of Euratom and EU policies. Besides a number of recommendations for incremental improvement of the JRC, the Panel has flagged that the JRC is in a unique position as a provider of independent scientific evidence inside the European Commission, but, because of this, the JRC and its research work are less visible to the outside world than they merit. The Panel also flags that the JRC and its stakeholders, internal and external to the Commission, would also benefit from more communication and interactions. The Panel has particularly appreciated the meetings with the stakeholders that gave much insight into the cooperation between the JRC and the other parts of the Commission, supporting our positive assessment and our suggestions for improvement.
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| 5. |
- Stattin, Pär, et al.
(författare)
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Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:1, s. 125-134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance. Objective: To investigate the association between radical local treatment and mortality in men with very high-risk PCa. Design, setting, and participants: Semiecologic study of men aged < 80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998-2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50-200 ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level < 50 ng/ml, any N, and M0) were used as positive controls. Intervention: Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis. Outcome measurements and statistical analysis: PCa and all-cause mortality rate ratios (MRRs). Results and limitations: Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28-0.95; and all-cause MRR: 0.56; 95% CI, 0.33-0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposurewere in agreement with results fromrandomized trials (PCaMRR: 0.75; 95% CI, 0.60-0.94; and all-cause MRR: 0.85; 95% CI, 0.72-1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity. Conclusions: The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective. Patient summary: Menwith very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality. (C) 2016 European Association of Urology. Published by Elsevier B.V.
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| 6. |
- Thomsen, Frederik B., et al.
(författare)
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Clinical characteristics and primary management of patients diagnosed with prostate cancer between 2007 and 2013 : status from a Danish primary referral center
- 2016
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 55:12, s. 1456-1460
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Danish Cancer Registry holds information on all prostate cancers (PCa) cases, including diagnostic TNM. However, stratification according to contemporary risk classification is not possible because histopathological grading and prostate-specific antigen (PSA) level are not registered. The objective of the study was to report clinical characteristics and primary management of men diagnosed with PCa from a primary referral center in Denmark. Material and methods: Records on all men diagnosed with PCa at the Department of Urology, Frederiksberg Hospital, 1 January 2007 - 31 December 2013, were reviewed. Clinical characteristics and primary treatment were recorded. The National Comprehensive Cancer Network risk group classification was used. Results: A total of 1934 men with a median age of 69 years (interquartile range 65-75) were diagnosed with PCa in the study period resulting in an incidence rate (World Standard Population) of 84/100 000. Overall, 18% were classified as low-risk, 34% as intermediate-risk, 23% as high-risk, 8% as very high-risk and 17% had metastatic disease at diagnosis. Among men age <65 years 70% had low-or intermediate-risk disease, while this was the case for 58% of men aged 65-75 and 22% of men aged >75. Metastatic disease was found in 11% of men <65 years, 17% of men 65-75 years and 23% of men >75 years. In total 73% of men with low-risk PCa were managed on watchful waiting or active surveillance. Curatively intended treatment was performed in 56% of men with intermediate-risk and 61% of men with high-risk PCa, while hormonal therapy was used in 90% of men with very high-risk and 98% of men with metastatic PCa. Conclusion: In a population without systematic PSA testing we found a large proportion of patients presenting with advanced PCa at diagnosis. Elderly patients presented with more advanced disease. Curative treatment was primarily used in younger men with clinically localized PCa.
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| 7. |
- Thomsen, S., et al.
(författare)
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Bringing evidence to policy to achieve health-related MDGs for all: justification and design of the EPI-4 project in China, India, Indonesia, and Vietnam
- 2013
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9880 .- 1654-9716. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- have shown substantial improvements in many countries. These statistics may be misleading, however, and may divert resources from disadvantaged populations within the same countries that are showing progress. The purpose of this article is to set out the relevance and design of the ‘‘Evidence for Policy and Implementation project (EPI-4)’’. EPI-4 aims to contribute to the reduction of inequities in the achievement of health-related MDGs in China, India, Indonesia and Vietnam through the promotion of researchinformed policymaking. Methods: Using a framework provided by the Commission on the Social Determinants of Health (CSDH), we compare national-level MDG targets and results, as well as their social and structural determinants, in China, India, Indonesia and Vietnam. Results: To understand country-level MDG achievements it is useful to analyze their social and structural determinants. This analysis is not sufficient, however, to understand within-country inequities. Specialized analyses are required for this purpose, as is discussion and debate of the results with policymakers, which is the aim of the EPI-4 project. Conclusion: Reducing health inequities requires sophisticated analyses to identify disadvantaged populations within and between countries, and to determine evidence-based solutions that will make a difference. The EPI-4 project hopes to contribute to this goal.
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| 8. |
- Went, Molly, et al.
(författare)
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Deciphering the genetics and mechanisms of predisposition to multiple myeloma
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.
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