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- Chadeau-Hyam, M., et al.
(författare)
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Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:5, s. 1065-1072
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.METHODS:We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.RESULTS:Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.CONCLUSIONS:This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
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| 3. |
- Bergdahl, Johan, et al.
(författare)
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Evaluation of an algorithm ascertaining cases of osteonecrosis of the jaw in the Swedish National Patient Register
- 2013
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Ingår i: Clinical Epidemiology. - Macclesfield : Dove Medical Press Ltd.. - 1179-1349 .- 1179-1349. ; 5:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteonecrosis of the jaw (ONJ) is a medical condition associated with antiresorptive drugs, among others, used to treat osteoporosis and bone metastasis. Currently, there is no consensus regarding the definition of ONJ, and no ONJ-specific International Classification of Diseases-10 code exists. Therefore, register-based studies of this condition may be troublesome.Purpose: To evaluate an algorithm ascertaining ONJ cases in an attempt to facilitate future assessments of ONJ in clinical and epidemiological studies.Methods: By means of the Patient Register and the Prescribed Drug Register, we identified all postmenopausal female residents in Sweden from 2005 through 2009. To identify potential cases of ONJ, we employed an algorithm including the following conditions: periapical abscess with sinus, inflammatory conditions of jaws, alveolitis of jaws, idiopathic aseptic necrosis of bone, osteonecrosis due to drugs, osteonecrosis due to previous trauma, other secondary osteonecrosis, other osteonecrosis, and unspecified osteonecrosis. Women seen at departments of oral and maxillofacial surgery, with at least one of the conditions, were classified as potential cases of ONJ. Conditions in anatomic sites other than the jaw were excluded. Validation was performed through medical record review. Case confirmation was based on the ONJ definition by the American Association of Oral and Maxillofacial Surgeons. The algorithm was evaluated by positive predictive values (PPVs) stratified by diagnosis.Results: For the 87 potential cases identified through our algorithm, the medical records were obtained for 83. The overall PPV was 18% (95% confidence interval (CI) 10%–28%). The highest PPV was observed in osteonecrosis due to drugs (83%, 95% CI 36%–100%). Several diagnoses had a PPV of 0 or were not used at all (periapical abscess with sinus, alveolitis of jaws, idiopathic aseptic necrosis of bone, osteonecrosis due to previous trauma, other secondary osteonecrosis, other osteonecrosis, and unspecified osteonecrosis).Conclusion: It was possible to ascertain cases of ONJ from the Swedish registers using this algorithm; however, the PPV was low. Thus, further refinements of the algorithm are necessary. © 2013 Bergdahl et al, publisher and licensee Dove Medical Press Ltd.
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- Hebels, Dennie G. A. J., et al.
(författare)
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Performance in omics analyses of blood samples in long-term storage : opportunities for the exploitation of existing biobanks in environmental health research
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:4, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Background: The suitability for omic analysis of biosamples collected in previous decades and currently stored in biobanks is unknown.Objectives: We evaluated the influence of handling and storage conditions of blood-derived biosamples on transcriptomic, epigenomic (CpG methylation), plasma metabolomic [UPLC-ToFMS (ultra performance liquid chromatography-time-of-flight mass spectrometry)], and wide-target proteomic profiles.Methods: We collected fresh blood samples without RNA preservative in heparin, EDTA, or citrate and held them at room temperature for ≤ 24 hr before fractionating them into buffy coat, erythrocytes, and plasma and freezing the fractions at -80oC or in liquid nitrogen. We developed methodology for isolating RNA from the buffy coats and conducted omic analyses. Finally, we analyzed analogous samples from the EPIC-Italy and Northern Sweden Health and Disease Study biobanks.Results: Microarray-quality RNA could be isolated from buffy coats (including most biobank samples) that had been frozen within 8 hr of blood collection by thawing the samples in RNA preservative. Different anticoagulants influenced the metabolomic, proteomic, and to a lesser extent transcriptomic profiles. Transcriptomic profiles were most affected by the delay (as little as 2 hr) before blood fractionation, whereas storage temperature had minimal impact. Effects on metabolomic and proteomic profiles were noted in samples processed ≥ 8 hr after collection, but no effects were due to storage temperature. None of the variables examined significantly influenced the epigenomic profiles. No systematic influence of time-in-storage was observed in samples stored over a period of 13-17 years.Conclusions: Most samples currently stored in biobanks are amenable to meaningful omics analysis, provided that they satisfy collection and storage criteria defined in this study.
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| 5. |
- Kelly, Rachel S., et al.
(författare)
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Blood erythrocyte concentrations of cadmium and lead and the risk of B-cell non-Hodgkin's lymphoma and multiple myeloma : a nested case-control study
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:11, s. Article Number: UNSP e81892-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for non-Hodgkin's lymphoma (NHL), a group of haematological malignancies with a suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether exposure was associated with risk of B-cell NHL and multiple myeloma. Methods: 194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and the Northern Sweden Health and Disease Study. Cases were matched to healthy controls by centre, age, gender and date of blood collection. Cd and Pb were measured in blood samples provided at recruitment using inductively coupled plasma-mass spectrometry. Logistic regression was applied to assess the association with risk. Analyses were stratified by cohort and gender and by subtype where possible. Results: There was little evidence of an increased risk of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI 0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40) or Pb (B-cell NHL: 0.93 95% CI 0.43, 2.02, multiple myeloma: OR 1.63 95% CI 0.45, 5.94) in the total population when comparing the highest to the lowest quartile of exposure. However, gender and cohort specific differences in results were observed. In females the risk of B-cell NHL was more than doubled in those with a body burden of Cd >1 mu g/L (OR 2.20 95% CI; 1.04, 4.65). Conclusions: This nested case-control study does not support a consistent positive association between Cd or Pb and NHL, but there is some indication of a gender specific effect suggesting further research is warranted.
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