| 1. |
- Rydberg Sterner, Therese, et al.
(författare)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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| 2. |
- Angelstam, Per, et al.
(författare)
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Evidence-Based Knowledge Versus Negotiated Indicators for Assessment of Ecological Sustainability : The Swedish Forest Stewardship Council Standard as a Case Study
- 2013
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 42:2, s. 229-240
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Tidskriftsartikel (refereegranskat)abstract
- Assessing ecological sustainability involves monitoring of indicators and comparison of their states with performance targets that are deemed sustainable. First, a normative model was developed centered on evidence-based knowledge about (a) forest composition, structure, and function at multiple scales, and (b) performance targets derived by quantifying the habitat amount in naturally dynamic forests, and as required for presence of populations of specialized focal species. Second, we compared the Forest Stewardship Council (FSC) certification standards' ecological indicators from 1998 and 2010 in Sweden to the normative model using a Specific, Measurable, Accurate, Realistic, and Timebound (SMART) indicator approach. Indicator variables and targets for riparian and aquatic ecosystems were clearly under-represented compared to terrestrial ones. FSC's ecological indicators expanded over time from composition and structure towards function, and from finer to coarser spatial scales. However, SMART indicators were few. Moreover, they poorly reflected quantitative evidence-based knowledge, a consequence of the fact that forest certification mirrors the outcome of a complex social negotiation process.
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| 3. |
- Battram, Thomas, et al.
(författare)
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Appraising the causal relevance of DNA methylation for risk of lung cancer
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:5, s. 1493-1504
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.Methods: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer.Results: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk.Conclusions: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.
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| 4. |
- Bell, David, et al.
(författare)
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Forest restoration to attract a putative umbrella species, the white-backed woodpecker, benefited saproxylic beetles
- 2015
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Ingår i: Ecosphere. - 2150-8925 .- 2150-8925. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Umbrella species are often spatially demanding and have limited ability to adapt to environmental changes induced by human land-use. This makes them vulnerable to human encroachment. In Sweden, broadleaved trees are disadvantaged by forestry, and commercially managed forests are often deprived of dead wood. This has led to a situation where previously widespread top predators in saproxylic food webs, such as the white-backed woodpecker (Dendrocopos leucotos), have become species of conservation concern. The white-backed woodpecker is generally considered an umbrella species, and it has been linked to forests with large volumes of dead wood from broadleaved trees. In recent years, forest stands have been restored for the white-backed woodpecker, but post-treatment evaluations have rarely included other species that also occur in broad-leaved forests (co-occurring species). Many co-occurring species are saproxylic beetles. In this study, we collected saproxylic beetles and environmental data in restored and commercially managed forests to evaluate if habitat restoration for the white-backed woodpecker also benefited other species with similar habitat associations. We found that volumes of coarse woody debris were higher in restored than in commercially managed forests, and that a majority of man-made snags and downed logs were created from birch trees (Betula spp.). Most spruce trees (Picea abies) were extracted during forest restoration, and this opened up the forest canopy, and created stands dominated by broadleaved trees. Many saproxylic beetles were more common in restored forests, and there were significant differences in species composition between treatments. These differences were largely explained by species traits. Effects of sun-exposure were particularly important, but many beneficiary species were also linked to dead wood from broadleaved trees. Red-listed saproxylic beetles showed a similar pattern with more species and individuals in restored sites. The white-backed woodpecker is still critically endangered in Sweden, but important prey species are already responding to forest restoration at the stand level. We recognize that landscape-level improvements will be required to bring the white-backed woodpecker back, but also that the umbrella species concept can provide a useful framework for successful forest restoration as many co-occurring saproxylic beetle species seemingly benefitted from restoration for the white-backed woodpecker.
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| 5. |
- Dagnino, Sonia, et al.
(författare)
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Prospective identification of elevated circulating CDCP1 in patients years before onset of lung cancer
- 2021
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 81:13, s. 3738-3748
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer–related dysregulation of CDCP1 expression years before diagnosis.
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| 6. |
- Dimou, Niki, et al.
(författare)
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Cigarette Smoking and Endometrial Cancer Risk : observational and Mendelian Randomization Analyses
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:9, s. 1839-1848
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses.METHODS: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined.RESULTS: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer.CONCLUSIONS: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. IMPACT: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
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| 7. |
- Edsjö, Anders, et al.
(författare)
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Building a precision medicine infrastructure at a national level : The Swedish experience
- 2023
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Ingår i: Cambridge Prisms: Precision Medicine. - : Cambridge University Press. - 2752-6143. ; 1
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.
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| 8. |
- Feng, Xiaoshuang, et al.
(författare)
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Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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| 9. |
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| 10. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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