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  • 1
    Publication Date: 2018-04-17
    Description: One-half of the genes in the human genome contain alternative promoters, some of which generate products with opposing functions. Aberrant silencing or activation of such alternative promoters is associated with multiple diseases, including cancer, but little is known regarding the molecular mechanisms that control alternative promoter choice. The SHC1 gene encodes p46 Shc /p52 Shc and p66 Shc , proteins oppositely regulating anchorage-independent growth that are produced by transcription initiated from the upstream and downstream tandem promoters of SHC1 , respectively. Here we demonstrate that activation of these promoters is mutually exclusive on separate alleles in single primary endothelial cells in a heritable fashion, ensuring expression of both transcripts by the cell. Peripheral blood lymphocytes that do not transcribe p66 Shc transcribed p52 Shc biallelically. This distinct monoallelic transcription pattern is established by allele-specific chromosomal looping between tandem promoters, which silences the upstream promoter. Our results reveal a new mechanism to control alternative promoter usage through higher-order chromatin structure.
    Print ISSN: 0270-7306
    Electronic ISSN: 1098-5549
    Topics: Biology , Medicine
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  • 2
    ISSN: 0277-5387
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  G-I-N Conference 2012; 20120822-20120825; Berlin; DOCP058 /20120710/
    Publication Date: 2012-07-11
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
    Keywords: CANCER ; carcinoma ; SYSTEM ; HEPATOCELLULAR-CARCINOMA ; incidence ; liver ; POPULATION ; RISK ; RISKS ; GENE ; GENES ; FAMILY ; primary ; tumour ; MEMBER ; MEMBERS ; ASSOCIATION ; CANDIDATE GENE ; SUSCEPTIBILITY ; AGE ; ovarian cancer ; OVARIAN-CANCER ; CERVICAL-CANCER ; bladder cancer ; BLADDER-CANCER ; SWEDEN ; DATABASE ; SIR ; familial risk ; CARRIERS ; FAMILY-CANCER DATABASE ; bile duct ; BILE-DUCTS ; CHOLECYSTECTOMY ; GALLBLADDER-CANCER ; RELATIVES ; VIRAL-HEPATITIS
    Abstract: Background and aims: Familial risks in liver and biliary cancers have been assessed in small case control studies, usually based on reported, but not medically verified, cancers in family members. Thus the degree of familial clustering for these cancers remains to be established. Methods: The nationwide Swedish Family-Cancer Database was used, covering 10.2 million individuals for the years 1961-1998 from the Swedish Cancer Registry. Liver and biliary tract cancers were identified from 1121 offspring between the ages of 0 and 66 years and 17 131 parents. Standardised incidence ratios (SIRs) and 95% confidence intervals (Cls) were calculated for cancers in family members. Results: All cancers in the liver and biliary system showed a familial SIR of 1.65 (95% Cl 1.05- 2.46). This was mainly explained by a high risk for familial gall bladder cancer (SIR 5.21 (95% Cl 2.07-10.80)) and for familial primary liver cancer with hepatocellular carcinoma histology (SIR 4.69 (95% Cl 1.48-11.04)). For gall bladder and hepatocellular cancer, maternal transmission appeared to be favoured. Gall bladder cancer was associated with pancreatic cancer (SIR 2.39 (95% Cl 1.23-4.18)). Primary liver cancer was associated with cervical, urinary bladder, and endocrine gland tumours. Cancer in extrahepatic bile ducts was associated with ovarian cancer and that in ampulla of Vater with thyroid cancer; however, these associations may have been fortuitous. Conclusions: This study has provided the first data on familial clustering of liver and gall bladder cancers, based on medically confirmed records. The risks were so high that heritable factors were likely to contribute, possibly modified by environmental factors. The demonstration of candidate genes would help to further characterise the familial risks
    Type of Publication: Journal article published
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  • 6
    Keywords: brain ; CANCER ; Germany ; neoplasms ; PROSTATE ; COHORT ; DISEASE ; EPIDEMIOLOGY ; incidence ; RISKS ; SITE ; SITES ; meningioma ; PATIENT ; FAMILY ; primary ; renal ; tumour ; MEMBER ; MEMBERS ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; AGE ; etiology ; CERVICAL-CANCER ; prostate cancer ; PROSTATE-CANCER ; MELANOMA ; SWEDEN ; DATABASE ; SIR ; familial risk ; NATIONWIDE ; FAMILY-CANCER DATABASE ; CLUES ; CLUSTER ; clustering ; FEATURES ; ONCOLOGY ; ADULTS ; RE ; FAMILIES ; GLIOMA ; TESTICULAR CANCER ; HIPPEL-LINDAU-DISEASE ; astrocytoma ; brain tumour ; ependymoma ; FAMILY-MEMBER ; medulloblastoma ; primary neoplasm ; renal cancer ; SCIENCE
    Abstract: We used the nationwide Swedish Family-Cancer Database to analyse the association of histology-specific brain tumours with other cancers in family members. Among 0-68-year-old offspring, 9414 patients with brain tumours were identified from 1961 to 2000, of whom, 3387 parents were diagnosed with any primary neoplasm. Astrocytoma, meningioma and neurinoma were the main histological types. Increased standardised incidence ratios (SIRs) were found for brain tumours in association with cancers at sites that are known features in recognised syndromes, such as haemangioblastoma and renal cancer in von Hippel-Lindau disease. In addition, an association between astrocytoma and melanoma was recognised. Among as yet unknown clustering, neurinoma was associated with testicular cancer and myeloma; meningioma was associated with cervical cancer; astrocytoma was associated with prostate cancer; ependymoma was associated with breast cancer. Although some of these may feature a true tumour cluster, they need to be confirmed in another setting. (C) 2003 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 14728940
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  • 7
    Keywords: CANCER ; Germany ; RISK ; PATIENT ; RISK-FACTORS ; SUSCEPTIBILITY ; risk factors ; DATABASE ; familial risk ; RE ; RHEUMATOID-ARTHRITIS ; RISK-FACTOR ; ENGLAND
    Type of Publication: Journal article published
    PubMed ID: 18308735
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  • 8
    Keywords: age at onset, AUTOIMMUNE-DISEASE, AUTOIMMUNITY, CANCER, cancer registries, cancer risk, CANCER-RISK,
    Abstract: Background: Patients diagnosed with Crohn disease (CD) are known to be at an increased risk of bowel cancers and lymphoma. CD is an autoimmune disease and we hypothesize that the patients are predisposed to a wider spectrum of cancers. Patients and methods: A CD research database was constructed by identifying hospitalized CD patients from the Hospital Discharge Register and cancer patients from the Swedish Cancer Registry. Follow-up of 21 788 CD patients first hospitalized during the years 1964-2004 identified 1424 cancer cases. Standardized incidence ratios (SIRs) were calculated by comparing cancers in CD patients with subjects without CD. Results: In addition to the known sites, many additional sites were in excess in CD patients. These included liver, pancreatic, lung, prostate, testicular, kidney and skin (squamous cell) cancers; nonthyroid endocrine tumors and leukemia. The previously established sites showed the highest SIRs; however, SIRs 〉 2.0 were noted for the novel sites of the liver, testis and kidney. For testicular cancer, the SIR of seminoma was 2.74. Cancer risks were influences by age at first hospitalization for CD but whether the age effects were increasing or decreasing depending on the cancer type. Conclusions: This large study identified many novel subsequent cancers in CD patients
    Type of Publication: Journal article published
    PubMed ID: 18765463
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  • 9
    Keywords: CANCER ; LUNG ; LUNG-CANCER ; COHORT ; MORTALITY ; POPULATION ; RISK ; RISKS ; SITES ; PATIENT ; FAMILY ; SKIN ; ASSOCIATION ; BREAST ; LYMPHOMA ; OVARIAN-CANCER ; smoking ; MELANOMA ; SWEDEN ; cancer risk ; DATABASE ; HIGH-RISK ; TRENDS ; MANAGEMENT ; asthma ; REGISTRY ; FAMILIES ; cancer registries ; AUTOIMMUNE-DISEASES ; allergy ; CANCERS ; CANCER-RISK ; national databases ; 33 ; TIMES ; ADULT ASTHMA
    Abstract: Asthma is an increasingly common disorder, affecting 5-10% of the population. It involves a dysregulated immune function, which may predispose to subsequent cancer. We examined cancer risk among Swedish subjects who had hospital admission once or multiple times for asthma. An asthma research database was created by identifying asthma patients from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. A total of 140 425 patients were hospitalised for asthma during 1965-2004, of whom 7421 patients developed cancer, giving an overall standardised incidence ratio (SIR) of 1.36. A significant increase was noted for most sites, with the exception of breast and ovarian cancers and non-Hodgkin's lymphoma and myeloma. Patients with multiple hospital admissions showed a high risk, particularly for stomach (SIR 1.70) and colon (SIR 1.99) cancers. A significant decrease was noted for endometrial cancer and skin melanoma. Oesophageal and lung cancers showed high risks throughout the study period, whereas stomach cancer increased towards the end of the period. The relatively stable temporal trends suggest that the asthmatic condition rather than its medication is responsible for the observed associations. British Journal of Cancer (2009) 100, 829-833. doi: 10.1038/sj.bjc.6604890 www.bjcancer.com Published online 27 January 2009 (C) 2009 Cancer Research UK
    Type of Publication: Journal article published
    PubMed ID: 19174822
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  • 10
    Keywords: CANCER ; tumor ; CELL ; FOLLOW-UP ; DISEASE ; EPIDEMIOLOGY ; RISK ; RISKS ; TUMORS ; PATIENT ; kidney ; FAMILY ; SKIN ; LYMPHOMA ; AGE ; leukemia ; SWEDEN ; cancer risk ; DATABASE ; HIGH-RISK ; SKIN-CANCER ; fibrosis ; REGISTRY ; FAMILIES ; cancer registries ; INCREASED RISK ; CANCERS ; CANCER-RISK ; SQUAMOUS-CELL ; SARCOIDOSIS ; SWEDISH ; UK ; national databases ; subsequent cancer ; HOSPITALIZATIONS ; PULMONARY SARCOIDOSIS
    Abstract: Background: Sarcoidosis patients show dysregulated immune function, which may be related to subsequent cancer. We examined here the overall and specific cancer risks among Swedish subjects who had been hospitalized for sarcoidosis. Methods: A sarcoidosis research database was created by identifying hospitalized sarcoidosis patients from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. Standardized incidence ratios (SIRs) were calculated for cancers in sarcoidosis patients compared with subjects without sarcoidosis. Results: A total of 10 037 patients were hospitalized for sarcoidosis during years 1964-2004. Among them 1045 patients developed subsequent cancer, giving an overall SIR of 1.40 and 1.18 for cancer diagnosed later than 1 year of follow-up. A significant excess was noted for skin (squamous cell), kidney and nonthyroid endocrine tumors and additionally for non-Hodgkin's lymphoma and leukemia. Patients with multiple hospitalizations showed high risks. Conclusions: A 40% overall excess incidence of cancer was noted among sarcoidosis patients, but the increase was confined mainly to the first year after hospitalization. However, the increased risks of skin cancer and non-Hodgkin's lymphoma and leukemia, especially for those with multiple hospitalizations or hospitalized at old age, call for clinical attention
    Type of Publication: Journal article published
    PubMed ID: 19211624
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