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Search Results: 1 - 10 of 157 matches for " Haukur Gunnarsson "
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The risk allele of SNP rs3803662 and the mRNA level of its closest genes TOX3 and LOC643714 predict adverse outcome for breast cancer patients
Gudmundsdottir Eydis Th,Barkardottir Rosa B,Arason Adalgeir,Gunnarsson Haukur
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-621
Abstract: Background The minor allele of SNP rs3803662 has been shown to correlate with increased breast cancer risk and with lower expression of TOX3. The SNP is closely located to TOX3 residing within an uncharacterised gene LOC643714. The aim of the study was to examine the association of the risk allele with expression of TOX3 and LOC643714, and of mRNA levels and genotype with clinical and pathological characteristics. Methods The SNP was genotyped in DNA isolated from blood and normal tissue from 160 breast cancer patients and mRNA levels were measured by microarrays and quantitative real-time (qRT)-PCR in breast tumours. Association with clinical and pathological characteristics was analysed by parametric tests. Results An association of the risk allele of rs3803662 with lower TOX3 expression was confirmed in oestrogen receptor (ER) positive tumours. It was more often observed in lobular tumours (p = 0.04), and carriers of the risk allele who had been diagnosed with luminal A tumours had shorter overall survival (OS) than carriers of the non-risk allele (p = 0.01). Positive correlation between the mRNA levels of TOX3 and LOC643714 was observed (r = 0.44 and p < 0.001). Association analysis with tumour pathology showed that low TOX3 and LOC643714 expression correlated with high Ki67 levels (p = 0.026 and p = 0.002) and the basal subtype (p < 0.001 and p < 0.001), whereas high expression correlated with ER (p = 0.004 and p < 0.001) and progesterone receptor (PgR) (p = 0.005 and p < 0.001) expression. Furthermore, high TOX3 and LOC643714 correlated with positive lymph nodes (p < 0.001 and p = 0.01). Patients with ER positive tumours and high levels of TOX3 mRNA had shorter overall- and distant metastasis free-survival (p = 0.017 and p = 0.021), an effect mostly attributable to patients with luminal B tumours. Conclusions The results suggest that the effect of the risk allele of rs3803662 is strongest in luminal A tumours and that the expression levels of TOX3 and/or LOC643714 affect the progression of breast cancer. The effect may vary depending on the subtype and developmental stage of the tumour.
Evidence against PALB2 involvement in Icelandic breast cancer susceptibility
Haukur Gunnarsson, Adalgeir Arason, Elizabeth M Gillanders, Bjarni A Agnarsson, Gudrun Johannesdottir, Oskar Johannsson, Rosa B Barkardottir
Journal of Negative Results in BioMedicine , 2008, DOI: 10.1186/1477-5751-7-5
Abstract: Breast cancer is among the most frequent human cancers and the most common carcinoma in women in the Western world, where one out of every ten women is affected. A dominant pattern of inheritance is evident in approximately 5–10% of all breast cancers. To date, two main breast cancer susceptibility genes have been identified; BRCA1 and BRCA2 accounting for nearly half of high-incidence breast cancer families and an increased relative risk of breast cancer by 10- to 20- fold [1,2]. Other known breast cancer susceptibility genes such as CHEK2 and ATM have a more moderate penetrance with an increased lifetime risk of about 2- to 3- fold [2].The PALB2 gene is a BRCA2 binding factor that ensures BRCA2 function as a tumor suppressor and has been shown to cause Fanconi anemia subtype FA-N when biallelic germ-line mutations occur in the gene [3-5]. Recent studies have reported several mutations in PALB2 to be associated with an increased risk of breast cancer [6-9]. One is the founder mutation 1592delT which has been found to be present at a significantly elevated frequency in breast cancer families in Finland, resulting in a 4-fold increased risk to mutation carriers [6]. Although predisposing PALB2 mutations generally appear to cause moderate risk of breast cancer [8], mutations have also been found in strong hereditary breast cancer families [7,9] and might thus be worthwhile searching for by linkage analysis in e.g. geographically confined populations.Only two BRCA1 and BRCA2 mutations have been found in the Icelandic population, BRCA2 999del5 and BRCA1 G5193A, both being founder mutations explaining a large proportion of familial breast cancer in Iceland [10]. The BRCA2 999del5 mutation is much more frequent, accounting for around 40% of the hereditary cases and found in about 8% of unselected breast cancer cases and 0,4% of population based control [11]. A BRCA2 999del5 mutation is also the most frequently occurring BRCA1/2 mutation in Finland [12], and haplotype anal
High-resolution genomic and expression analyses of copy number alterations in HER2-amplified breast cancer
Johan Staaf, G?ran J?nsson, Markus Ringnér, Johan Vallon-Christersson, Dorthe Grabau, Adalgeir Arason, Haukur Gunnarsson, Bjarni A Agnarsson, Per-Olof Malmstr?m, Oskar Johannsson, Niklas Loman, Rosa B Barkardottir, ?ke Borg
Breast Cancer Research , 2010, DOI: 10.1186/bcr2568
Abstract: Genome-wide DNA copy number profiling, using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH), and global gene expression profiling were performed on 200 and 87 HER2+ tumors, respectively. Genomic Identification of Significant Targets in Cancer (GISTIC) was used to identify significant copy number alterations (CNAs) in HER2+ tumors, which were related to a set of 554 non-HER2 amplified (HER2-) breast tumors. High-resolution oligonucleotide aCGH was used to delineate the 17q12-q21 region in high detail.The HER2-amplicon was narrowed to an 85.92 kbp region including the TCAP, PNMT, PERLD1, HER2, C17orf37 and GRB7 genes, and higher HER2 copy numbers indicated worse prognosis. In 31% of HER2+ tumors the amplicon extended to TOP2A, defining a subgroup of HER2+ breast cancer associated with estrogen receptor-positive status and with a trend of better survival than HER2+ breast cancers with deleted (18%) or neutral TOP2A (51%). HER2+ tumors were clearly distinguished from HER2- tumors by the presence of recurrent high-level amplifications and firestorm patterns on chromosome 17q. While there was no significant difference between HER2+ and HER2- tumors regarding the incidence of other recurrent high-level amplifications, differences in the co-amplification pattern were observed, as shown by the almost mutually exclusive occurrence of 8p12, 11q13 and 20q13 amplification in HER2+ tumors. GISTIC analysis identified 117 significant CNAs across all autosomes. Supervised analyses revealed: (1) significant CNAs separating HER2+ tumors stratified by clinical variables, and (2) CNAs separating HER2+ from HER2- tumors.We have performed a comprehensive survey of CNAs in HER2+ breast tumors, pinpointing significant genomic alterations including both known and potentially novel therapeutic targets. Our analysis sheds further light on the genomically complex and heterogeneous nature of HER2+ tumors in relation to other subgroups of breast cancer.Gene a
Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families
Adalgeir Arason, Haukur Gunnarsson, Gudrun Johannesdottir, Kristjan Jonasson, P?r-Ola Bendahl, Elizabeth M Gillanders, Bjarni A Agnarsson, G?ran J?nsson, Katri Pylk?s, Aki Mustonen, Tuomas Heikkinen, Kristiina Aittom?ki, Carl Blomqvist, Beatrice Melin, Oskar TH Johannsson, P?l M?ller, Robert Winqvist, Heli Nevanlinna, ?ke Borg, Rosa B Barkardottir
Breast Cancer Research , 2010, DOI: 10.1186/bcr2608
Abstract: GWS was performed using 811 microsatellite markers providing about five centiMorgan (cM) resolution. Multipoint logarithm of odds (LOD) scores were calculated using parametric and nonparametric methods. For selected markers and cases, tumour tissue was compared to normal tissue to look for allelic loss indicative of a tumour suppressor gene.The three highest signals were located at chromosomes 6q, 2p and 14q. One family contributed suggestive LOD scores (LOD 2.63 to 3.03, dominant model) at all these regions, without consistent evidence of a tumour suppressor gene. Haplotypes in nine affected family members mapped the loci to 2p23.2 to p21, 6q14.2 to q23.2 and 14q21.3 to q24.3. No evidence of a highly penetrant locus was found among the remaining families. The heterogeneity LOD (HLOD) at the 6q, 2p and 14q loci in all families was 3.27, 1.66 and 1.24, respectively. The subset of 13 Nordic families showed supportive HLODs at chromosome 6q (ranging from 0.34 to 1.37 by country subset). The 2p and 14q loci overlap with regions indicated by large families in previous GWS studies of breast cancer.Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.Increased susceptibility to breast cancer (BC) has been shown to be caused by germline segregation of three different classes of alleles: 1) high-penetrance genes with rare risk variants, 2) moderate-penetrance genes, also with rare variants and 3) low-penetrance alleles of common frequency [1]. Hereditary BC, defined by a significant familial aggregation of BC and explaining approximately 5 to 10% of cases diagnosed with BC, is as yet seen to arise from the first allele class whenever the causative gene is known. Genetic counselling c
Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics
G?ran J?nsson, Johan Staaf, Johan Vallon-Christersson, Markus Ringnér, Karolina Holm, Cecilia Hegardt, Haukur Gunnarsson, Rainer Fagerholm, Carina Strand, Bjarni A Agnarsson, Outi Kilpivaara, Lena Luts, P?ivi Heikkil?, Kristiina Aittom?ki, Carl Blomqvist, Niklas Loman, Per Malmstr?m, H?kan Olsson, Oskar Th Johannsson, Adalgeir Arason, Heli Nevanlinna, Rosa B Barkardottir, ?ke Borg
Breast Cancer Research , 2010, DOI: 10.1186/bcr2596
Abstract: We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer.We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis.Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may pro
The conceptualisation of health and disease in veterinary medicine
Stefan Gunnarsson
Acta Veterinaria Scandinavica , 2006, DOI: 10.1186/1751-0147-48-20
Abstract: Veterinary textbooks in several disciplines were investigated, but only textbooks with explicit definitions of the concepts were selected for examination.Eighty out of the 500 relevant books within veterinary medicine were written for non-veterinarians. Eight percent of the books had an explicit definition of health and/or disease. More frequently, textbooks written for non veterinarians did have definitions of health or disease, compared to textbooks written for professionals. A division of health definitions in five different categories was suggested, namely:1. Health as normality, 2. Health as biological function, 3. Health as homeostasis, 4. Health as physical and psychological well-being and 5. Health as productivity including reproduction.Few veterinary textbooks had any health or disease definition at all. Furthermore, explicit definitions of health stated by the authors seemed to have little impact on how health and disease are handled within the profession. Veterinary medicine would probably gain from theoretical discussions about health and disease.The concept of health, as well as the concept of disease, must be regarded as essential to veterinary medicine. Nevertheless, it appears to be uncommon that broader discussions about these basic concepts occur within the veterinary society. The increasing diagnostic possibilities to identify diseases make it crucial to define disease and health, as this basic distinction gives the very fundament of disease classification.The naive definition of health in veterinary medicine seems to be that health is no more than the very absence of disease, which can be considered as a dichotomous definition. This position is often the case for basic assumptions in e.g. epidemiology, where the disease frequency commonly is calculated based on that disease is binary, which means that either the animal has the disease or it does not have the disease.The epidemiological methods used to investigate the excellence of a disease test,
The conceptualisation of health and disease in veterinary medicine
Gunnarsson Stefan
Acta Veterinaria Scandinavica , 2006, DOI: 10.1186/1751-0147-47-71
Abstract: Background The concept of health, as well as the concept of disease, is central in veterinary medicine. However, the definitions "health" and "disease" are not generally acknowledged by veterinarians. The aim of this study was to examine how the concepts "health" and "disease" are defined in veterinary textbooks. Methods Veterinary textbooks in several disciplines were investigated, but only textbooks with explicit definitions of the concepts were selected for examination. Results Eighty out of the 500 relevant books within veterinary medicine were written for non-veterinarians. Eight percent of the books had an explicit definition of health and/or disease. More frequently, textbooks written for non veterinarians did have definitions of health or disease, compared to textbooks written for professionals. A division of health definitions in five different categories was suggested, namely: 1. Health as normality, 2. Health as biological function, 3. Health as homeostasis, 4. Health as physical and psychological well-being and 5. Health as productivity including reproduction. Conclusion Few veterinary textbooks had any health or disease definition at all. Furthermore, explicit definitions of health stated by the authors seemed to have little impact on how health and disease are handled within the profession. Veterinary medicine would probably gain from theoretical discussions about health and disease.
Documenting Freedom From Disease And Re-Establishing a Free Status After a Breakdown Aleutian Disease (Plasmacytosis) in Farmed Mink in Iceland
Gunnarsson Eggert
Acta Veterinaria Scandinavica , 2001, DOI: 10.1186/1751-0147-42-s1-s87
Abstract:
The First Swede in Space:The Making of a Public Science Hero
Andreas Gunnarsson
Culture Unbound : Journal of Current Cultural Research , 2009,
Abstract: The first Swede in space, Christer Fuglesang, has become an iconic figure for the popularisation of science in Sweden. Named as Sweden’s first astronaut in 1992, Fuglesang remained a relatively anonymous and somewhat derisory figure prior to his space launch in 2006. After his space mission, however, Fuglesang has become the very personification of science in Swedish society. In this paper, the transformation of Fuglesang’s public persona and his construction as a Swedish public science hero is analysed in detail. It is discussed how after 2006, Fuglesang can be seen as providing confirmation, both of the existence of a cultural gap separating science from society, and of the ability of certain heroic individuals to bridge this gap in a way that renders it more appreciable to a larger public.In the main part of the paper, three aspects of Fuglesang’s elevation into a Swedish public science hero are discussed: First, the cyborg metaphor is used to analyse the fearlessness Fuglesang expresses towards yielding to, and entering into close communion with science and technology. Second, the transcendence of earthly perspective aspired to by science for so long, and apparently realized through space travel, is discussed in relation to Fuglesang’s personal experiences of space. Third, the inseparability of Fuglesang’s nationality from his heroism is discussed. It was only through the repeated flagging of his Swedishness that Fuglesang’s routine space mission gained any particular significance enabling it to be communicated as a major scientific event.Finally, closer attention is paid to the scientific message Fuglesang is delivering to Swedish society. It is argued that he acts to promote renewed faith and confidence in the ability of science to open up new horizons for the future. The task of the public science hero is to help enable these new horizons to colonize the public imagination.
Electron self-energy in A3C60 (A=K, Rb): Effects of t1u plasmon in GW approximation
O. Gunnarsson
Physics , 1997, DOI: 10.1088/0953-8984/9/26/011
Abstract: The electron self-energy of the t1u states in A3C60 (A=K, Rb) is calculated using the so-called GW approximation. The calculation is performed within a model which considers the t1u charge carrier plasmon at 0.5 eV and takes into account scattering of the electrons within the t1u band. A moderate reduction (35 %) of the t1u band width is obtained.
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