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Sökning: WFRF:(Bernstein L.)

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221.
  • Ho, Joshua W. K., et al. (författare)
  • Comparative analysis of metazoan chromatin organization
  • 2014
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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225.
  • Lee, Eunjung, et al. (författare)
  • Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk.
  • 2015
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.METHODS: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.RESULTS: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.CONCLUSIONS: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus.IMPACT: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus. Cancer Epidemiol Biomarkers Prev; 24(11); 1801-3. ©2015 AACR.
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226.
  • Leibovitzh, Haim, et al. (författare)
  • Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis
  • 2023
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:8, s. 1462-1471
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay.RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all).CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.
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227.
  • Levine, David M, et al. (författare)
  • A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma.
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228.
  • Lindberg, L. J., et al. (författare)
  • Risk of Synchronous and Metachronous Colorectal Cancer : Population-Based Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50
  • 2019
  • Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969 .- 1799-7267. ; 108:2, s. 152-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases. Material and Methods: Based on data from national Danish cancer registers, we estimated the proportion of synchronous colorectal cancer and the incidence rates and risks for metachronous colorectal cancer in 28,504 individuals, who developed 577 metachronous colorectal cancer above age 50. Results: Synchronous colorectal cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal cancer was associated with sex, tumor location, and age with the strongest influence from the latter. The incidence rate ratios for metachronous colorectal cancer ranged from above 6 in patients below age 65 to <1–3.2 in patients above age 65. The absolute risk of metachronous colorectal cancer was ⩾10% in patients below age 65 and 1.0%–8.0% in patients above age 65. Conclusion: Individuals who develop sporadic, non-inherited colorectal cancer above age 50 are at a significantly increased risk of metachronous colorectal cancer with risk estimates that are strongly affected by age. This observation underscores the need for development of targeted surveillance in the most common clinical subset of colorectal cancer.
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229.
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230.
  • Mikocka-Walus, Antonina, et al. (författare)
  • Exploring the Relationship Between Self-Isolation and Distress Among People with Gastrointestinal Disorders During the COVID-19 Pandemic
  • 2022
  • Ingår i: Journal of clinical psychology in medical settings. - : Springer. - 1068-9583 .- 1573-3572. ; 29:3, s. 654-665
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to explore the association between perceived isolation and symptoms of distress in people with GI disorders at the time of the pandemic; and to examine factors which moderate this relationship. This online cross-sectional survey was advertised in May-September 2020 via patient organisations and associated social media. Overall, 831 people (82% female, mean age 49 years) from 27 countries participated. A significant relationship between social isolation and psychological distress was noted (r = .525, p < .001). GI symptoms moderated the association between isolation and distress (B = .047, t = 2.47, p = .015). Interventions targeting these factors may help to reduce distress in people with GI disorders at the time of major stressors such as the COVID-19 pandemic.
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