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Sökning: WFRF:(Svenson Ulrika)

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  • Henckel, E., et al. (författare)
  • Telomere length was similar in school-age children with bronchopulmonary dysplasia and allergic asthma
  • 2018
  • Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 107:8, s. 1395-1401
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Inflammation is a major factor in the pathophysiology of bronchopulmonary dysplasia (BPD), and it contributes to accelerated telomere shortening and cellular ageing. This study aimed to determine its effect on telomere length and lung function in school-aged children born preterm with BPD.Methods: We examined 29 children with BPD, born preterm in Stockholm county 1998-99, along with 28 children with allergic asthma born at term matched for age and gender. At 10 years of age, we measured relative telomere length (RTL) in blood by quantitative polymerase chain reaction, lung function by spirometry and inflammation by fractional exhaled nitric oxide and blood cytokines.Results: RTL was not different in preterm born with BPD compared to term born children with asthma. The gender effect was strong in both groups; girls had significantly longer median RTL than boys (1.8 versus 1.5, p < 0.01). Short RTL was associated with low forced expiratory flow, also after adjusting for gender, but was not affected by severity of BPD or ongoing inflammation.Conclusion: Telomere length was similar in 10-year-old children born preterm with a history of BPD and term born children with allergic asthma. However, impaired lung function and male gender were associated wrth short telomeres.
  • Mansouri, Larry, et al. (författare)
  • Short telomere length is associated with NOTCH1/SF3B1/TP53 aberrations and poor outcome in newly diagnosed chronic lymphocytic leukemia patients
  • 2013
  • Ingår i: American Journal of Hematology. - : John Wiley and Sons. - 0361-8609 .- 1096-8652. ; 88:8, s. 647-651
  • Tidskriftsartikel (refereegranskat)abstract
    • Most previous studies on telomere length (TL) in chronic lymphocytic leukemia (CLL) are based on referral cohorts including a high proportion of aggressive cases. Here, the impact of TL was analyzed in a population-based cohort of newly diagnosed CLL (n=265) and in relation to other prognostic markers. Short telomeres were particularly associated with high-risk genetic markers, such as NOTCH1, SF3B1, or TP53 aberrations, and predicted a short time to treatment (TTT) and overall survival (OS) (both P<0.0001). TL was an independent prognostic factor and subdivided patients with otherwise good-prognostic features (e.g., mutated IGHV genes, favorable cytogenetics) into subgroups with different outcome. Furthermore, in follow-up samples (n=119) taken 5-8 years after diagnosis, TL correlated well with TL at diagnosis and remained unaffected by treatment. Altogether, these novel data indicate that short TL already at diagnosis is associated with poor outcome in CLL and that TL can be measured at later stages of the disease. Am. J. Hematol. 88:647-651, 2013. (c) 2013 Wiley Periodicals, Inc.
  • Sjögren, Per, et al. (författare)
  • Stand up for health-avoiding sedentary behaviour might lengthen your telomeres : secondary outcomes from a physical activity RCT in older people
  • 2014
  • Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group. - 0306-3674 .- 1473-0480. ; 48:19, s. 1407-1409
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Telomere length has been associated with a healthy lifestyle and longevity. However, the effect of increased physical activity on telomere length is still unknown. Therefore, the aim was to study the relationship between changes in physical activity level and sedentary behaviour and changes in telomere length. Methods Telomere length was measured in blood cells 6 months apart in 49, 68-year-old, sedentary, overweight individuals taking part in a randomised controlled physical activity intervention trial. The intervention group received individualised physical activity on prescription. Physical activity was measured with a 7-day diary, questionnaires and a pedometer. Sitting time was measured with the short version of The International Physical Activity Questionnaire. Results Time spent exercising as well as steps per day increased significantly in the intervention group. Reported sitting time decreased in both groups. No significant associations between changes in steps per day and changes in telomere length were noted. In the intervention group, there was a negative correlation between changes in time spent exercising and changes in telomere length (rho=-0.39, p=0.07). On the other hand, in the intervention group, telomere lengthening was significantly associated with reduced sitting time (rho=-0.68, p=0.02). Conclusions Reduced sitting time was associated with telomere lengthening in blood cells in sedentary, overweight 68-year-old individuals participating in a 6-month physical activity intervention trial.
  • Svenson, Ulrika, et al. (författare)
  • Blood cell telomere length is a dynamic feature
  • 2011
  • Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 6:6, s. e21485-
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a considerable heterogeneity in blood cell telomere length (TL) for individuals of similar age and recent studies have revealed that TL changes by time are dependent on TL at baseline. TL is partly inherited, but results from several studies indicate that e.g. life style and/or environmental factors can affect TL during life. Collectively, these studies imply that blood cell TL might fluctuate during a life time and that the actual TL at a defined time point is the result of potential regulatory mechanism(s) and environmental factors. We analyzed relative TL (RTL) in subsequent blood samples taken six months apart from 50 individuals and found significant associations between RTL changes and RTL at baseline. Individual RTL changes per month were more pronounced than the changes recorded in a previously studied population analyzed after 10 years' follow up. The data argues for an oscillating TL pattern which levels out at longer follow up times. In a separate group of five blood donors, a marked telomere loss was demonstrated within a six month period for one donor where after TL was stabilized. PCR determined RTL changes were verified by Southern blotting and STELA (single telomere elongation length analysis). The STELA demonstrated that for the donor with a marked telomere loss, the heterogeneity of the telomere distribution decreased considerably, with a noteworthy loss of the largest telomeres. In summary, the collected data support the concept that individual blood cell telomere length is a dynamic feature and this will be important to recognize in future studies of human telomere biology.
  • Varadi, Verena, et al. (författare)
  • Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis
  • 2009
  • Ingår i: European Journal of Cancer. - Oxford : Elsevier. - 1879-0852 .- 0959-8049. ; 45:17, s. 3008-3016
  • Tidskriftsartikel (refereegranskat)abstract
    • Telomeres are essential structures for maintaining chromosomal stability and their length has been reported to correlate with cancer risk and clinical outcome. Single nucleotide polymorphisms (SNPs) in genes encoding telomere-associated proteins could affect telomere length and chromosomal stability by influencing gene expression or protein configuration in the telomeres. Here, we report the results of the first association study on genetic variation in telomere-associated genes and their effect on telomere length, breast cancer (BC) susceptibility and prognosis. We genotyped 14 potentially functional and most informative SNPs in nine telomere-associated genes (TERT, TEP1, TERF1, TERF2, TERF21p, ACD, POT1, TNKS and TNKS2) in 782 incident BC cases and 1559 matched controls. Relative telomere length (RTL) varied statistically significantly between the genotypes of the SNPs rs446977 (TEP1, p = 0.04), rs938886 (TEP1, p = 0.04) and rs6990097 (TNKS, p = 0.04). However, none of them was associated with BC susceptibility and only rs6990097 correlated with regional lymph node metastasis (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.08-1.77). The strongest association with BC susceptibility was observed for rs3785074 (TERF2, OR 0.51, 95% CI 0.31-0.83) and rs10509637 (TNKS2, OR 1.33, 9S% CI 1.08-1.62). Haplotype and diplotype analysis confirmed the association of the TNKS2 gene with BC susceptibility. rs3785074 (TERF2) was additionally associated with histologic grade (OR 1.44, 95% CI 1.08-1.92) and negative oestrogen receptor status (OR 2.93, 95% CI 1.13-7.58). None of the SNPs showed a significant correlation with survival of the breast cancer patients. With these results, none of the SNPs represents any valuable prognostic marker for BC. (C) 2009 Elsevier Ltd. All rights reserved.
  • Haycock, Philip C., et al. (författare)
  • Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
  • 2017
  • Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
  • Köhn, Linda, et al. (författare)
  • Specific Genomic Aberrations Predict Survival, But Low Mutation Rate in Cancer Hot Spots, in Clear Cell Renal Cell Carcinoma
  • 2015
  • Ingår i: Applied immunohistochemistry & molecular morphology (Print). - 1541-2016 .- 1533-4058. ; 23:5, s. 334-342
  • Tidskriftsartikel (refereegranskat)abstract
    • Detailed genetic profiling of clear cell renal cell carcinoma (ccRCC) has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. VHL and PBRM1, both located at chromosome 3p, are 2 major genes mutated at high frequency but apart from these aberrations, the mutational landscape in ccRCC is largely undefined. Potential prognostic information given by the genomic changes appears to depend on the particular cohort studied. We analyzed a Swedish ccRCC cohort of 74 patients and found common changes (loss or gain occurring in >20% of the tumors) in 12 chromosomal regions (1p, 3p, 3q, 5q, 6q, 7p, 7q 8p, 9p, 9q, 10q, and 14q). A poor outcome was associated with gain of 7q and losses on 9p, 9q, and 14q. These aberrations were more frequent in metastasized tumors, suggesting alterations of genes important for tumor progression. Sequencing of 48 genes implicated in cancer revealed that only VHL, TP53, and PTEN were mutated at a noticeable frequency (51%, 9%, and 9%, respectively). Shorter relative telomere length (RTL) has been associated with loss of specific chromosomal regions in ccRCC tumors, but we could not verify this finding. However, a significantly lower tumor/nontumor (T/N) RTL ratio was detected for tumors with losses in 4q or 9p. In conclusion, poor outcome in ccRCC was associated with gain of 7q and loss on 9p, 9q, and 14q, whereas the mutation rate overall was low in a screen of cancer-associated genes.
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